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1 School of Medical Sciences, Division of Biosciences, RMIT University, PO Box 71, Bundoora 3083, Melbourne, Victoria, Australia2 Institute of Biomedical Research, University of Sydney, Sydney, NSW 2006, Australia3 Howard Florey Institute, University of Melbourne, Melbourne, Victoria, VIC 3010, Australia
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Abstract |
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(Received 29 September 2005;
accepted after revision 18 November 2005; first published online 18 November 2005)
Corresponding author E. Badoer: School of Medical Sciences, Division of Biosciences, RMIT University, PO Box 71, Bundoora 3083, Melbourne, Victoria, Australia. Email: emilio.badoer{at}rmit.edu.au
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Introduction |
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The paraventricular nucleus of the hypothalamus (PVN) is a key integrative nucleus in the forebrain mediating neuroendocrine responses (Swanson & Sawchenko, 1980; Coote, 1995; Badoer, 1996, 2001). Additionally, it is clear that activation of the PVN can elicit changes in blood pressure and heart rate that are also mediated by changes in sympathetic nerve activity (Kannan et al. 1987; Dampney, 1994; Coote, 1995; Dampney et al. 2000; Deering & Coote, 2000; Badoer, 2001; Badoer et al. 2002). The PVN projects strongly to the RVLM (Luiten et al. 1985; Shafton et al. 1998; Pyner & Coote, 2000), and this pathway contributes to the changes in sympathetic nerve activity observed following activation of the PVN. Thus, neurotransmitters that can influence the activity of those PVN neurones that project to the RVLM have the potential to influence basal resting sympathetic tone.
ATP mediates its main actions as a neurotransmitter via activation of P2-purinoceptors (Burnstock, 1980, 1996, 1997), of which there are two major classes, namely, the P2Y and P2X purinoceptors. P2Y purinoceptors are G-protein-coupled purinoceptors, while P2X purinoceptors are ligand-gated ion channels (Burnstock & Kennedy, 1985; Dubyak, 1991; Fredholm et al. 1994; Harden et al. 1995). Based on expression cloning of the purinoceptors in various different cell lines, seven different subtypes of P2X purinoceptors (P2X1–P2X7) have been identified (Buell et al. 1996). These different P2X purinoceptor subtypes have been differentiated by the rate of desensitization, agonist/antagonist selectivity, permeation properties and sensitivity to changes in the extracellular pH (Buell et al. 1996; King et al. 1997; North, 2002). There are seven subtypes of P2X purinoceptors, but only P2X1–P2X6 purinoceptors are believed to be involved in the fast excitatory synaptic transmission between neurones (Edwards et al. 1992; Evans et al. 1992; Ueno et al. 1992, 1999). P2X7 purinoceptors were believed to play a role in apoptosis and were thought to be mainly found on cells involved in immune function (Collo et al. 1997). More recent studies, however, indicate that P2X7 purinoceptors may influence neurotransmission (Deuchars et al. 2001; Sperlach et al. 2002). Recently, though, the nature of the P2X7 purinoceptor labelling in the brain has been questioned (Sanchez-Noguiero et al. 2005).
Numerous studies utilizing autoradiography, in situ hybridization and immunohistochemistry have been employed to demonstrate the widespread distribution of P2X purinoceptors in many regions of the brain, including the hypothalamus (Bo & Burnstock, 1994; Collo et al. 1996; Vulcanova et al. 1996, 1997; Tuyau et al. 1997; Kanjhan et al. 1999; Yao et al. 2000, 2001). ATP applied to rat hypothalamic neurones has been shown to induce a rapid increase in intracellular calcium concentration (Chen et al. 1994). Indeed, microinjections of ATP into the PVN of the hypothalamus can induce the release of arginine-vasopressin (Mori et al. 1992). In addition, electrophysiological studies have also provided evidence that indicates the use of ATP as a transmitter by the caudal brainstem noradrenergic neurones in their interaction with vasopressinergic neurosecretory cells in the hypothalamic supraoptic nucleus (Buller et al. 1996). Thus, these studies strongly indicate the presence of functional purinoceptors in the hypothalamic nuclei.
Despite the increasing evidence to support the presence of the various P2X purinoceptor subtypes in the hypothalamus, their distribution has not been examined in great detail. At present, it is unclear whether PVN neurones that project to the RVLM also contain P2X purinoceptors. Such a pathway would provide an anatomical framework for purinergic neurotransmission to influence the tonic generation of sympathetic nerve activity. In light of this, the aim of the present study was to examine whether P2X1–P2X6 purinoceptors were located on the PVN neurones, which project directly to the RVLM.
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Methods |
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Twenty-four male Sprague–Dawley rats (Monash University Animal Services, Victoria, Australia) weighing 200–250 g were housed in the Animal Facility (RMIT University, Victoria, Australia), where rat chow and tap water were available ad libitum. All of the experimental protocols used in this study were performed in accordance with the Prevention of Cruelty to Animals Act 1986 and were approved by the RMIT University Animal Ethics committee. All the experiments conform to the guidelines set out by the National Health and Medical Research Council of Australia. Every attempt was made to minimize animal suffering and discomfort and to reduce the number of animals needed to obtain reliable results.
Rat retrograde tracer microinjection
The rats were anaesthetized with sodium pentobarbitone (60 mg kg–1, I.P.; Nembutal, Boehringer Ingelheim, North Ryde NSW 2123, Australia). Buscopan compositum (0.03 ml kg–1, S.C.; consisting of a mixture of hyoscine-N-butyl bromide (12.5 mg kg–1) and 0.1 mg kg–1 dipyrone, Boehringer Ingelheim) was also administered immediately prior to surgery to minimize salivary secretions.
Prior to locating the RVLM, the right femoral artery was cannulated and connected to a pressure transducer to enable arterial blood pressure (ABP) to be monitored. The rat was placed prone and its head mounted in a Kopf stereotactic frame. An incision through the scalp was made to expose the lambda and bregma and a partial craniotomy of the occipital bone performed. A burr hole, approximately 4 mm in diameter, was drilled into the skull overlying the RVLM on the left side and the dura mater cleared. The stereotactic coordinates of the RVLM were 1.8–2.2 mm left of the sagittal suture, 2.5–3.5 mm caudal to the lambdoid suture and 8.9 mm ventral to the dural surface (Paxinos & Watson, 1986; Kantzides & Badoer, 2003). The pressor region of the RVLM was then located by injecting 25–50 nl ofL-glutamate (0.1 M, Sigma, St Louis, MO, USA) using a glass micropipette. An increase of approximately 20 mmHg in the ABP identified the region of the RVLM. The micropipette was carefully removed from the brain, emptied and then filled with the retrogradely transported tracer, rhodamine-tagged microspheres (1:1 dilution with 0.9% sterile saline; LumaFluor, Naples, FL, USA), and then reinserted into the pressor region of the RVLM. A unilateral injection of 250 nl of the tracer solution was made over 10 min, and the micropipette was left in place for several minutes following completion of the injection to avoid tracer leakage along the route of the pipette. Upon the removal of the micropipette, the scalp was sutured and the arterial cannula removed. Oxytetracycline (200 mg kg–1S.C.; Terramycin, Provet, Melbourne, Victoria, Australia) was administered to prevent infection and buprenorphine hydrochloride (15 µg I.P.; Temgesic, Reckitt and Colman Pharmaceuticals, Sydney, NSW, Australia) was administered for analgesia.
Rats were housed for 2 weeks following the surgical procedure to allow for the transport of the retrograde tracer before they were deeply anaesthetized with sodium pentobarbitone (60 mg kg–1, I.P.) and transcardially perfused with approximately 350–400 ml of heparinized phosphate-buffered saline (PBS), followed by 4% paraformaldehyde (PFA) in phosphate buffer (PB) (0.1 M, pH 7.4). The perfusion pressure was maintained at about 100–120 mmHg. Brains were then carefully removed and postfixed in 4% PFA–PB solution for 2 h, then transferred into 20% sucrose in PB overnight.
The following day, hypothalamic sections, of 40 µm thickness, were cut on a cryostat and alternate serial sections encompassing the PVN were collected from each rat. For this study, a maximum of three P2X purinoceptor subtypes were studied in each rat and seven rats were used for the group data for each P2X purinoceptor subtype.
Immunohistochemistry
Sections of the PVN from the rats injected with rhodamine-tagged microspheres underwent three 5 min washes in PB and were incubated with 10% normal horse serum (NHS) in PBS for 60 min at room temperature. The sections were incubated free-floating and processed using standard immunohistochemical procedures as previously described (Kantzides & Badoer, 2003). Primary antibodies of sheep anti-P2X1, P2X3, P2X4, P2X5 and P2X6, and rabbit anti-P2X2, were diluted 1:1000 in PB containing 2% NHS and 0.3% Triton X-100, and the free-floating sections incubated for 24 h at room temperature.
Following three 5 min washes in PB, the tissue was incubated for 1 h at room temperature with the appropriate biotinylated secondary antibody (biotinylated antigoat for P2X1, P2X3, P2X4, P2X5 and P2X6 or biotinylated antirabbit for P2X2, Sigma-Aldrich, Australia) diluted to 1:600. After washing off unbound secondary antibodies in three 5 min washes in PB, the sections were incubated for 1 h at room temperature using Extravidin (1:400 in 0.1 M PB, Sigma-Aldrich, Australia).
Following three 5 min washes in 0.05 M Tris buffer (pH 7.6), the sections were incubated for 10 min at room temperature with 0.05% 3,3'-diaminobenzidine hydrochloride (DAB) and 40 mg nickel ammonium sulphate aqueous crystals in 100 ml 0.05 M Tris buffer). The reaction was initiated by the addition of 5 µl of 17.5% hydrogen peroxide (H2O2) (Biotech Pharm P/l, Australia) and terminated by washes with fresh 0.05 M Tris buffer. Sections were then washed, dried, dipped in xylene (Analar, Merck Pty Ltd, Australia) and mounted onto gelatine-subbed slides and coverslipped using DePex mounting medium (BDH, Poole, UK).
Microscopy of P2X purinoceptors and RVLM-projecting neurones
All sections processed immunohistochemically for P2X were examined under normal bright field illumination and fluorescence microscopy using a Leica DMLB microscope. Double-labelled neurones (P2X purinoceptor subtype + fluorescent tracer) were detected by rapidly switching between the two light sources. The PVN was determined according to the morphology and histology of the area and confirmed by the location of the RVLM-projecting neurones, which approximately delineate the boundaries of the PVN (Shafton et al. 1998).
Quantification
The RVLM-projecting neurones and double-labelled neurones for each P2X purinoceptor subtype were counted in each section. These sections represented five different levels that encompassed the full rostral–caudal extent of the PVN. The numbers of double-labelled neurones were expressed as a percentage of the total number of RVLM-projecting neurones in each section and the means ±S.E.M. were determined for each level of the PVN. The overall percentage of double-labelled neurones in the PVN for each of the P2X purinoceptor subtypes was also determined.
Statistical analysis
Comparisons between the percentages of double-labelled neurones were performed using completely randomized one-way ANOVA. The statistical software package used was GB-STAT version 7.0 (Dynamic Microsystems Inc., Silver Spring, MD, USA), and the level of significance was set at P < 0.05.
Mapping
For accurate illustration of the different levels of the PVN, maps were drawn from each of the five rostral to caudal levels. Digital files were generated using the software package MD Plot (version 4.0) and an MD3 microscope digitizer stage (Minnesota Datametric Corporation, Shoreview, MN, USA) attached to a Leica DMLB microscope.
Photomicroscopy
Images were acquired using a digital camera (Sensi Cam, PCO CCD Imaging, Kelheim, Germany) on an Olympus BX60 microscope. The digital images obtained were imported into Metamorph Imaging version 4.6 (Universal Imaging Corp., Downingtown, PA, USA), and only the contrast and lightness were modified for presentation purposes.
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Immunohistochemical staining for P2X1–P2X6 purinoceptor subtypes revealed a widespread distribution throughout the rostral–caudal levels of the PVN (Fig. 1). Although the number of P2X immunoreactive neurones was not quantified, it was apparent that the major proportion of the P2X purinoceptors was present in the parvocellular regions of the PVN, including the dorsal, medial and lateral subnuclei, where neurones that project to the RVLM are known to be abundantly located (Fig. 1).
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The RVLM-projecting neurones were found distributed throughout the rostral–caudal extent of the PVN. The number of RVLM-projecting neurones and their distribution were quantified in five rostral–caudal levels of the PVN (Fig. 2). The distribution profile of RVLM-projecting neurones appeared as a bell-shaped curve, with the maximum number in the mid-rostral–caudal level of the PVN (Figs 3 and 4). The distribution pattern of the retrogradely labelled neurones was similar for each of the different P2X purinoceptor subtypes analysed. The total number of RVLM-projecting neurones counted in each series of sections ranged from 147 ± 14 for the P2X1 subtype to 255 ± 22 for the P2X5 subtype. A summary of these data is shown in Table 1. There were no significant differences found in the number of RVLM-projecting neurones in each group (Table 1).
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In general, retrogradely labelled neurones that were positive for a particular P2X purinoceptor subtype were observed throughout the rostral–caudal extent of the PVN. The distribution profile for double-labelled neurones for each P2X purinoceptor subtype followed a bell-shaped curve, with the peak occurring in the mid-rostral–caudal level of the PVN, and was similar to the distribution profile of the RVLM-projecting neurones (Figs 3 and 4).
The average proportion of RVLM-projecting neurones in the PVN that contained a particular P2X purinoceptor subtype ranged from 14% for P2X1 to 29% for P2X3 (Table 1). Overall, there was a significant difference in the proportion of RVLM-projecting neurones containing a specific P2X purinoceptor subtype (P < 0.05, overall one-way ANOVA). Comparison of the means and adjusting for multiple comparisons indicated that the overall difference was due primarily to a significant difference between neurones containing P2X1 and those containing P2X3 (P < 0.05, comparison of means adjusted with Bonferroni's correction, Table 1).
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Discussion |
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Distribution of P2X purinoceptors in the hypothalamic PVN
In the present work, P2X1–P2X6 purinoceptor subtypes were detected throughout the PVN, including the dorsal parvocellular and medial parvocellular PVN, areas known to contain PVN neurones that project to the RVLM. The most important finding of the present study was the discovery of the presence of P2X purinoceptors on neurones in the PVN that project to the RVLM. The rostral–caudal distribution profiles of the double-labelled neurones were found to be a broad bell-shaped pattern that was similar to the distribution profile of the RVLM-projecting neurones in the PVN. However, we found that varying proportions of P2X purinoceptor subtypes were present on the PVN neurones projecting to RVLM. The proportions of these PVN neurones that contained each purinoceptor subtype varied from 14% for P2X1 to 29% for P2X3, and this difference was statistically significant. These results suggest that there is a distinct distribution of the different P2X purinoceptor subtypes in the PVN regions that contain neurones projecting to the RVLM. Furthermore, when the average percentages of double-labelled neurones for each of the P2X subtypes were added together, their sum exceeded 100%. This indicates that more than one P2X purinoceptor subtype must be present on a PVN neurone that projects to the RVLM. This may be explained by observations that P2X purinoceptor subtypes can operate as heteromers (e.g. P2X2 and P2X3) as well as homomers (Balcar et al. 1995; Worthington et al. 1999a,b).
In the present study, we found that P2X1–P2X6 purinoceptors were abundantly distributed throughout the hypothalamus, and for this reason we did not attempt to quantify them. However, our observations support previous reports indicating the presence of purinoceptors in the brain (Bo & Burnstock, 1994; Balcar et al. 1995; Vulcanova et al. 1997; Kidd et al. 1998; Kanjhan et al. 1999; Yao et al. 2000). Early studies of the distribution of the different subtypes of purinoceptors suggested that P2X2, P2X4 and P2X6 were the predominant forms in the CNS (Collo et al. 1996; Kanjhan et al. 1999). More recent studies, however, indicate that all subtypes are present within the CNS (Yao et al. 2000). The distribution of P2X1–P2X6 purinoceptors has been extensively studied in the medulla and pons (Yao et al. 2000). By contrast, the distribution of these purinoceptors in the more rostral brain regions, including the hypothalamus, with the exception of P2X2, has not been examined in great detail (Yao et al. 2003).
Significance
Activation or inhibition of the PVN can elicit marked changes in blood pressure, heart rate and renal sympathetic nerve activity (Kannan et al. 1987; Coote, 1995; Badoer et al. 2002). The neurones in the PVN that project to the RVLM undoubtedly mediate some of the changes seen in sympathetic nerve activity. Since the RVLM is an important brain region involved in the tonic regulation of sympathetic nerve activity (Ross et al. 1984; Dampney et al. 2000), altering the activity of neuronal inputs into the RVLM could have important functional implications. Thus, activation of PVN neurones that project to the RVLM by stimulating P2X purinoceptors could contribute to the influence of the PVN on resting sympathetic nerve activity (Potter & White, 1980; Dampney, 1994; Dampney et al. 2000; Badoer et al. 2002).
The effect of stimulating or inhibiting P2X purinoceptors in the PVN has been studied in one report to date, in which ATP injected into the PVN did not affect basal blood pressure whilst injection of the P2X purinoceptor antagonist, suramin, did not affect the pressor response to peripheral chemoreceptor stimulation (Kubo et al. 1997). These experiments were performed in spinally transected, anaesthetized rats. Thus, effects on the sympathetic nervous system could not be evaluated. In light of the present work, the effects of stimulation and antagonism of purinoceptors in the PVN on the sympathetic nervous system requires further investigation.
Methodological considerations
The antibodies used in the present study have been raised against the extracellular domain of each P2X purinoceptor subtype found in the rat. The domains chosen were unique to each P2X purinoceptor subtype to ensure no cross-reactivity. The antibodies recognize a single P2X purinoceptor subtype, and antibody specificity has been described in great detail previously (Hansen et al. 1997, 1999a,b; Worthington et al. 1999a,b; Yao et al. 2000, 2001, 2003; Sluyter et al. 2001).
We injected the retrogradely transported tracer into the pressor region of the RVLM. We identified this region functionally to maximize the probability of labelling the neurones in the PVN that were involved in the regulation of sympathetic nerve activity. This injection site was confirmed histologically and the injections were similar in spread, and covered the rostral–caudal extent of the RVLM, hence the similarity in the number of fluorescent neurones between the groups.
Summary and conclusion
We have described the distribution of P2X1–P2X6 purinoceptors in the hypothalamic PVN. We determined, in detail, the rostral–caudal distribution of these P2X purinoceptor subtypes on PVN neurones that project to the pressor region of the RVLM and found significant differences between the proportion of P2X purinoceptors located on the PVN neurones. Furthermore, our quantitative analysis also indicates that there is likely to be several different P2X purinoceptor subtypes present on the same neurones in the PVN. Finally, our observations of P2X purinoceptor subtypes found on the PVN neurones projecting to the RVLM suggests that ATP may function as an important neurotransmitter in influencing neurones projecting from the PVN to RVLM; hence, ATP within the PVN may have an important role in the regulation of sympathetic nerve activity.
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References |
|---|
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Badoer E (2001). Hypothalamic paraventricular nucleus and cardiovascular regulation. Cin Exp Pharmacol Physiol 28, 95–99.
Badoer E, Ng CW & Matteo RD (2002). Tonic sympathoinhibition arising from the hypothalamic PVN in the conscious rabbit. Brain Res 947, 17–24.[CrossRef][Medline]
Balcar VJ, Li Y, Killinger S & Bennett MR (1995). Autoradiography of P2x ATP receptors in the rat brain. Br J Pharmacol 115, 302–306.
Bo X & Burnstock G (1994). Distribution of [3H]
,ß-methylene ATP binding sites in rat brain and spinal cord. Neuroreport 5, 1601–1604.[Medline]
Buell G, Collo G & Rassendren F (1996). P2X receptors: An emerging channel family. Eur J Neuroscience 8, 2221–2228.[CrossRef][Medline]
Buller K, Khanna S, Sibbald J & Day T (1996). Central noradrenergic neurons signal via ATP to elicit vasopressin responses to haemorrhage. Neuroscience 73, 637–642.[CrossRef][Medline]
Burnstock G (1980). Purinergic nerves and receptors. Progressive Biochem Pharmacol 16, 141–154.
Burnstock G (1996). Purinergic neurotransmission. Seminars Neurosciences 8, 171–257.
Burnstock G (1997). The past, present and future of purine nucleotides as signalling molecules. Neuropharmacology 36, 1127–1338.[CrossRef][Medline]
Burnstock G & Kennedy C (1985). Is there a basis for distinguishing two types of P2-purinoceptor?Gen Pharmacol: Vascular System 16, 433–440.[CrossRef]
Chen ZP, Levy A & Lightman SL (1994). Activation of specific ATP receptors induces a rapid increase in intracellular calcium ions in rat hypothlamic neurons. Brain Res 641, 249–256.[CrossRef][Medline]
Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA & Buell G (1997). Tissue distribution of the P2X7 receptor. Neuropharmacology 36, 1277–1283.[CrossRef][Medline]
Collo G, North RA, Kawashima E, Merlo-Pich E, Neidhart S, Surprenant A & Buell G (1996). Cloning of P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. J Neuroscience 16, 2495–2507.
Coote JH (1995). Cardiovascular function of the paraventricular nucleus of the hypothalamus. Biol Signals 4, 142–149.[Medline]
Dampney RAL (1994). Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74, 323–364.
Dampney RAL, Tagawa T, Horiuchi J, Potts PD, Fontes M & Polson JW (2000). What drives the tonic activity of presympathetic neurons in the rostral ventrolateral medulla?Clin Exp Pharmacol Physiol 27, 1049–1053.[CrossRef][Medline]
Deering J & Coote JH (2000). Paraventricular neurons elicit a volume expansion-like change in sympathetic nerves to the heart and kidney in the rabbit. Exp Physiol 85, 177–186.[Abstract]
Deuchars SA, Atkinson L, Brooke REHM, Milligan CJ, Batten TFC, Buckley NJ, Parson SH & Deuchars J (2001). Neuronal P2X7 receptors are targetted to presynaptic terminals in the central and peripheral nervous systems. J Neuroscience 21, 7143–7152.
Dubyak GR (1991). Signal transduction by P2-purinergic receptors for extracellular ATP. Am J Respir Cell Mol Biol 4, 295–300.[Medline]
Edwards FA, Gibb AJ & Colquhoun D (1992). ATP receptor mediated synaptic currents in the central nervous system. Nature 359, 144–147.[CrossRef][Medline]
Evans RJ, Derkach V & Surprenant A (1992). ATP mediates fast synaptic transmission in mammalian neurons. Nature 357, 503–505.[CrossRef][Medline]
Fredholm BB, Abbrachio MP, Burnstock G, Daly JW, Harden TK, Jacobson KA, Leff P & Williams M (1994). Nomenclature and classification of purinoreceptors. Pharmacol Rev 46, 143–156.[Medline]
Granata AR, Ruggiero DA, Park DH, Joh TH & Reis DJ (1985). Brainstem area with C1 epinephrine neurons mediates baroreflex vasodepressor responses. Am J Physiol 248, H547–H567.[Medline]
Hansen MA, Barden JA, Balcar VJ, Keay KA & Bennett MR (1997). Structural motif and characteristics of the extracellular domain of P2X receptors. Biochem Biophys Res Comm 236, 670–675.[CrossRef][Medline]
Hansen MA, Bennett MR & Barden JA (1999a). Distribution of purinergic P2X receptors in the rat heart. J Auton Nerv Syst 78, 1–9.[CrossRef][Medline]
Hansen MA, Dutton JL, Balcar VJ, Barden JA & Bennett MR (1999b). P2X (purinergic) receptor distributions in rat blood vessels. J Auton Nerv Syst 75, 147–155.[CrossRef][Medline]
Harden TK, Boyer JL & Nicholas RA (1995). P2-purinergic receptors: subtype signalling responses and structure. Ann Rev Pharmacol Toxicol 35, 541–579.[CrossRef][Medline]
Hirooka Y, Polson JW, Potts PD & Dampney RAL (1997). Hypoxia-induced Fos expression in neurons projecting to the pressor region of the rostral ventrolateral medulla. Neurosci 80, 1209–1224.[CrossRef][Medline]
Kanjhan R, Housley GD, Burton LD, Christie DL, Kippenberger A, Thorne PF, Luo L & Ryan A (1999). Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system. J Comp Neurol 407, 11–32.[CrossRef][Medline]
Kannan H, Hayashida Y & Yamashita H (1987). Increase in sympathetic outflow by paraventricular nucleus stimulation in awake rats. Am J Physiol 256, R1325–R1330.
Kantzides A & Badoer E (2003). Fos, RVLM-projecting neurons, and spinally projecting neurons in the PVN following hypertonic saline infusion. Am J Physiol Regul Integr Comp Physiol 284, 945–953.
Kidd EJ, Miller KJ, Sansum AJ & Humphrey PPA (1998). Evidence for P2X3 receptors in the developing rat brain. Neuroscience 87, 533–539.[CrossRef][Medline]
King BF, Wildman SS, Ziganshina LE, Pintor J & Burnstock G (1997). Effects of extracellular pH on agonism and antagonism at a recombinant P2X2 receptor. Br J Pharmacol 121, 1445–1453.[CrossRef][Medline]
Kubo T, Yanagihara Y, Yamaguchi H & Fukumori R (1997). Excitatory amino acid receptors in the paraventricular hypothalamic nucleus mediate pressor response induced by carotid body chemoreceptor stimulation in rats. Clin Exp Hypertens 19, 1117–1134.[Medline]
Luiten PGN, ter Horst GJ, Karst H & Steffens AB (1985). The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord. Brain Res 329, 374–378.[CrossRef][Medline]
Mori M, Tsushima H & Matsuda T (1992). Antidiuretic effects of purinoreceptor agonists injected into the hypothalamic paraventricular nucleus of water-loaded, ethanolanesthetized rats. Neuropharmacology 31, 585–592.[Medline]
North RA (2002). Molecular physiology of P2X receptors. Physiol Rev 82, 1013–1067.
Paxinos G & Watson C (1986). The Rat Brain in Stereotaxic Coordinates. Academic Press Ltd, London.
Polson JW, Potts PD, Li Y-W & Dampney RAL (1995). Fos expression in neurones projecting to the pressor region in the rostral ventrolateral medulla after sustained hypertension in conscious rabbits. Neuroscience 67, 107–123.[CrossRef][Medline]
Potter P & White TD (1980). Release of adenosine 5'-triphosphate from the synaptosomes from different regions of rat brain. Neuroscience 5, 1351–1356.[CrossRef][Medline]
Pyner S & Coote JH (2000). Identification of branching paraventricular neurons of the hypothalamus that project to the rostroventrolateral medulla and spinal cord. Neuroscience 100, 549–556.[CrossRef][Medline]
Ross CA, Ruggiero DA, Park DH, Joh TH, Sved AF, Fernandez-Pardel J, Saavedra JM & Reis DJ (1984). Tonic vasomotor control by the rostral ventrolateral medulla: effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin. J Neurosci 4, 474–494.[Abstract]
Sanchez-Noguiero J, Marin-Garcia P & Miras Portugal MT (2005). Characterisation of a functional P2X7-like receptor in cerebellar granule neurons from P2X7 knockout mice. FEBS Lett 579, 3783–3788.[CrossRef][Medline]
Shafton A, Ryan A & Badoer E (1998). Neurons in the hypothalamic paraventricular nucleus send collaterals to the spinal cord and to the rostral ventrolateral medulla in the rat. Brain Res 801, 239–243.[CrossRef][Medline]
Sluyter R, Barden JA & Wiley JS (2001). Expression of P2X purinergic receptors on human B-lymphocytes. Cell Tissue Res 304, 231–236.[CrossRef][Medline]
Sperlach B, Kofalvi K, Deuchars J, Atkinson L, Milligan CJ, Buckley NJ & Vizi ES (2002). Involvement of P2X7 receptors in the regulation of neurotransmitter release in rat hippocampus. J Neurochem 81, 1196–1121.[CrossRef][Medline]
Sun M-K & Spyer KM (1991). Responses of rostroventrolateral medulla spinal vasomotor neurons to the chemoreceptor stimulation in rats. J Auton Nerv Syst 33, 79–84.[Medline]
Swanson LW & Sawchenko PE (1980). Paraventricular nucleus: a site for the integration of neuroendocrine and autonomic mechanisms. Neuroendocrinology 31, 410–417.[Medline]
Tuyau M, Hansen MA, Coleman MJ, Dampney RAL, Balcar VJ & Bennett MR (1997). Autoradiography of [3H],ß-methylene-ATP binding sites in the medulla oblongata and spinal cord of the rat. Neurochem Int 30, 159–169.[CrossRef][Medline]
Ueno S, Harata N, Inoue K & Akaike N (1992). ATP-gated currents in dissociated rat nucleus solitarii neurons. J Neurophysiol 68, 778–785.
Ueno S, Tsuda M, Iwanaga T & Inoue K (1999). Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons. Br J Pharmacol 126, 429–436.[CrossRef][Medline]
Vulcanova L, Arvidsson U, Riedl M, Wang J, Buell G, Surprenant A, North RA & Elde R (1996). Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry. Proc Natl Acad Sci U S A 93, 8063–8067.
Vulcanova L, Riedl MS, Shuster SJ, Buell G, Surprenant A, North RA & Elde R (1997). Immunocytochemical study of the P2X2 and P2X3 receptor subtypes in rat and monkey sensory neurons on their central terminals. Neuropharmacology 36, 1229–1424.[CrossRef][Medline]
Worthington R, Arumugam T, Hansen M, Balcar V & Barden J (1999a). Identifcation and localisation of ATP P2X receptors in rat midbrain. Electrophoresis 20, 2077–2080.[CrossRef][Medline]
Worthington R, Hansen MA, Balcar VJ, Bennett MR & Barden JA (1999b). Analysis of novel P2X subunit-specific antibodies in rat cardiac and smooth muscle. Electrophoresis 20, 2081–2085.[Medline]
Yao ST, Barden JA, Finkelstein DI, Bennett MR & Lawrence AJ (2000). Comparative study on the distribution patterns of P2X1–P2X6 receptor immunoreactivity in the brainstem of the rat and the common marmoset (Callithrix jacchus): association with catecholamine cell groups. J Comp Neurol 427, 485–507.[CrossRef][Medline]
Yao ST, Barden JA & Lawrence AJ (2001). On the immunohistochemical distribution of ionotrophic P2X receptors in the nucleus tractus solitarius of the rat. Neuroscience 108, 673–685.[CrossRef][Medline]
Yao ST, Gourine AV, Spyer KM, Barden JA & Lawrence AJ (2003). Localisation of P2X2 receptor subunit immunoreactivity on nitric oxide synthase expressing neurones in the brain stem and hypothalamus of the rat: a fluorescence immunohistochemical study. Neuroscience 121, 411–419.[CrossRef][Medline]
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