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1 Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Medicinaregatan 15 D, Box 431, 405 30 Göteborg, Sweden
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Abstract |
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- and ß-adrenoceptor blockade. Both the CCK-A receptor antagonist lorglumide (48 mg kg–1, I.V.) and the CCK-B receptor antagonist itriglumide (5.5 mg kg–1, I.V.), given separately, prevented the expected increase in pentagastrin and, in addition, reduced the glandular protein synthesis by 16 and 12%, respectively, below the level of saline-treated rats. In rats treated with saline only, the glandular protein synthesis was reduced by 22% by the CCK-A receptor antagonist and by 17% by the CCK-B receptor antagonist; combined, the two antagonists caused no further reduction (20%). There was no increase in the glandular protein synthesis of pentagastrin-treated rats compared to that of the saline-treated rats when both groups of rats were exposed to a combination of the two types of CCK receptor antagonists. In pentagastrin-treated rats, the protein synthesis in the parotid glands was 23% less in the presence of the non-selective nitric oxide (NO) synthase inhibitor L-NAME (30 mg kg–1, I.V.) than in its absence; the result was the same (23%) when the neuronal NO synthase inhibitor N
-propyl-L-arginine (N-PLA; 30 mg kg–1, I.V.) replaced L-NAME. The protein synthesis in rats treated with saline only was not reduced by L-NAME; nor was the protein synthesis of saline-treated rats different from that of pentagastrin- and L-NAME-treated rats. Thus, under ‘basal’ conditions, a portion of the glandular protein synthesis, as well as the whole increase in synthesis in response to administration of pentagastrin, engaged both types of CCK receptors. Furthermore, NO generation, owing to neuronal NO synthase activity, was required for the increase to occur in response to pentagastrin, whereas a non-NO-dependent pathway was responsible for the protein synthesis under ‘basal’ conditions.
(Received 16 February 2006;
accepted after revision 23 March 2006; first published online 23 March 2006)
Corresponding author J. Ekström: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Medicinaregatan 15 D, Box 431, 405 30 Göteborg, Sweden. Email: jorgen.ekstrom{at}pharm.gu.se
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Introduction |
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In the present study, the effect of intravenous infusion of pentagastrin on the incorporation of [3H]leucine into trichloroacetic acid-insoluble material of the rat parotid gland, used as an index of protein synthesis, was investigated.
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Methods |
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A total of 114 adult female Sprague–Dawley rats (B & K Universal AB, Sollentuna, Sweden) were used. The animals were maintained on an ordinary pelleted diet (B & K Universal). They were fasted overnight, and the experiments started in the morning. All protocols were carried out according to local ethical committee guidelines.
The animals, divided into age- and weight-matched study groups, were subjected to: (1) saline (229 ± 10 g, n
= 6) or pentagastrin (229 ± 10 g, n
= 6); (2) saline (268 ± 5 g, n
= 5) or pentagastrin plus the CCK-A receptor antagonist lorglumide (257 ± 6 g, n
= 5); (3) saline (255 ± 9 g, n
= 4) or pentagastrin plus the CCK-B receptor antagonist itriglumide (255 ± 14 g, n
= 4); (4) saline (268 ± 5 g, n
= 5) or saline plus the CCK-A receptor antagonist (257 ± 6 g, n
= 5); (5) saline (275 ± 4 g, n
= 5) or saline plus the CCK-B receptor antagonist (276 ± 7 g, n
= 5); (6) saline (259 ± 3 g, n
= 4) or saline plus CCK-A and -B receptor antagonists (260 ± 2 g, n
= 4); (7) saline plus CCK-A and -B receptor antagonists (272 ± 4 g, n
= 5) or pentagastrin plus CCK-A and -B receptor antagonists (268 ± 4 g, n
= 5); (8) pentagastrin (265 ± 6 g, n
= 4) or pentagastrin plus the neuronal-type nitric oxide (NO) synthase inhibitor N-propyl-L-arginine (N-PLA; 262 ± 2 g, n
= 4); (9) pentagastrin (272 ± 4 g, n
= 4) or pentagastrin plus the non-selective NO synthase inhibitor L-NAME (271 ± 2 g, n
= 4); (10) saline (251 ± 7 g, n
= 5) or saline plus L-NAME (249 ± 7 g, n
= 5); (11) saline (272 ± 9 g, n
= 6) or pentagastrin plus L-NAME (271 ± 8 g, n
= 6); and (12) saline plus L-NAME (259 ± 4 g, n
= 4) or pentagastrin plus L-NAME (260 ± 4 g, n
= 4). In each study group, two rats were paired, based on age and body weight, before the experiment began, one to serve as experimental animal and the other as control animal. The pair of animals was treated concomitantly and in the same way apart from the difference in type of infusion (and pretreatment of drugs) and, furthermore, the glands of each pair were processed and analysed at the same time.
The animals were anaesthetized with pentobarbitone (50 mg kg–1, I.P., Apoteksbolaget; when required additional pentobarbitone was given intravenously), and then fitted with a tracheal cannula and a rectal probe to maintain the body temperature at 38°C using a thermostatically controlled blanket. The femoral vein was cannulated using a polyethylene catheter to provide a venous conduit. Atropine (Sigma), the -adrenoceptor antagonist phentolamine (Novartis) and the ß-adrenoceptor antagonist propranolol (Sigma) were injected intravenously (1 mg kg–1 of each) 5–10 min before the start of the infusion of pentagastrin or saline and, with respect to the adrenoceptor blockers, once again, 40 min later at the same dose. When appropriate, the CCK-A receptor antagonist lorglumide (48 mg kg–1, I.V., Sigma), or the CCK-B receptor antagonist itriglumide (5.5 mg kg–1, I.V., Sigma) or both antagonists were also administered about 5–10 min before the infusion (Makovec et al. 1987, 1999). To block the generation of NO, the highly selective inhibitor of neuronal type NO synthase, N-propyl-L-arginine (N-PLA, Tocris, Bristol, UK) and the non-selective NO synthase inhibitor L-NAME (Sigma) were used (Moncada, 1992; Zhang et al. 1997); these blockers were each given at a dose of 30 mg kg–1
I.V. and also here, 5–10 min before the start of the infusion. Pentagastrin (20 µg kg–1 h–1, I.V.) or saline was infused in a volume of 0.8 ml for 1 h. The dose of pentagastrin was chosen based on an earlier study (Çevik Aras & Ekström, 2006), where pentagastrin caused the release of protein from the parotid gland of the rat in vivo. The infusion period of 1 h may be compared with elevated gastrin levels over several hours when refeeding fasted animals (Kitano et al. 2000). Thirty minutes after the end of the infusion period, [3H]leucine (500 µCi kg–1 in 0.5 ml saline), from Amersham Biosciences, was injected intravenously. Fifteen minutes later, the abdomen was opened, the aorta cut and the animal exsanguinated. The parotid glands of both sides were rapidly removed, washed in saline, pressed gently between gauze pads, placed on filter paper to remove adherent tissue (if any) and to absorb additional fluid, weighed, frozen (–20°C) and stored (–70°C) until processed within a week.
Processing of tissues
Each gland was treated separately. After thawing, the gland was homogenized in 1 ml of cold 5 mM NaOH. Of the supernatant, two aliquots of 250 µl were used. The samples were diluted to 1 ml. To 100 µl of this solution, 500 µl of 5% trichloroacetic acid was added to precipitate the gland homogenate, and the mixture was centrifuged at 3000g for 5 min. This procedure was repeated twice; at the last centrifugation, the supernatant was virtually devoid of radioactivity. To the final precipitate, 500 µl Soluene 100 (Perkin Elmer, Boston, MA, USA) was added and left overnight; the blank consisted of 500 µl of Soluene 100. Then 8 ml Optiphase HiSafe 2 (Fisons Chemicals, Leicester, UK) was added, and the mixture was analysed in a scintillation counter (LKB Wallac, Perkin Elmer, Wellesley, MA, USA). The tests were made in duplicate. The amount of radiolabelled leucine was expressed as disintegrations per minute per milligram of gland tissue (d.p.m. min–1 (mg gland)–1).
Statistics
For each rat, a mean value (mg gland weight or d.p.m. min–1 (mg gland)–1) was calculated for left and right glands, which was used for statistical analyses. Statistical significance of difference was calculated using Student's paired t test and, as for d.p.m. min–1 (mg gland)–1, comparisons were based on log values. Probabilities of less than 5% were considered significant. Values presented are means ± S.E.M.
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Results |
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The gland weights of experimental rats and those rats serving as controls in the various groups were about the same, with the exception of the group comparing the effect of pentagastrin with that of pentagastrin plus N-PLA, in which a slightly significant difference occurred (9%, P < 0.05), see legends of Figs 1–5.
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Saline and pentagastrin with or without cholecystokinin receptor antagonists. Infusion of pentagastrin (20 µg kg–1 h–1) increased the incorporation of [3H]leucine into trichloroacetic acid-insoluble material of the parotid gland by 17% compared to the infusion of saline (P < 0.01; Fig. 1). In the presence of either the CCK-A receptor antagonist lorglumide (48 mg kg–1, I.V.) or the CCK-B receptor antagonist itriglumide (5.5 mg kg–1, I.V.), the parotid protein synthesis in the pentagastrin-treated rats was 16 and 12% lower than in the saline-treated rats (P < 0.01), respectively.
Saline with or without cholecystokinin receptor antagonists. Compared to the parotid protein synthesis in rats subjected to saline only, the protein synthesis in rats subjected to saline and the CCK-A receptor antagonist or to saline and the CCK-B antagonist was 22 (P < 0.05) and 17% lower (P < 0.01), respectively (Fig. 2). The two types of CCK receptor antagonists in combination lowered the protein synthesis in saline-treated rats by 20% (P < 0.05; Fig. 2).
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Saline and pentagastrin with L-NAME. The parotid protein synthesis was the same in the rats subjected to pentagastrin and L-NAME as in those subjected to saline alone. Thus, L-NAME prevented the expected increase in synthesis in response to pentagastrin but caused no further reduction (Fig. 5).
Comparisons in the presence of L-NAME between saline and pentagastrin. There was no difference in the parotid protein synthesis between the rats subjected to saline and L-NAME and those subjected to pentagastrin and L-NAME (Fig. 5).
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Discussion |
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- and ß-adrenoceptor antagonists (Çevik Aras & Ekström, 2006). The protein secretion evoked by pentagastrin was revealed by a subsequent intravenous wash-out injection of the muscarinic agonist methacholine, giving rise to a salivary response of increased protein concentration by about 150%, without any change in volume, compared to the methacholine-evoked salivary response in the absence of the preceding pentagastrin infusion. In the present study, in response to the same rate of infusion of pentagastrin over a period of 1 h and under blockade of the adrenoceptors as well as of the muscarinic receptors, the rate of [3H]leucine incorporation into trichloroacetic acid-insoluble material of the parotid gland, indicating protein synthesis, was found to be increased by 17% above the level of the glands in the control rats subjected to saline infusion alone. In the presence of either the CCK-A receptor blocker lorglumide or the CCK-B receptor blocker itriglumide, the expected response to pentagastrin was not only prevented but turned into a decrease, by 16 and 12%, respectively. Thus, both the pentagastrin-induced increase in protein synthesis and a part of the on-going ‘basal’ protein synthesis in the gland depended on the engagement of both types of CCK receptors. Further support for the idea that the ‘basal’ protein synthesis was influenced by stimuli exerting their actions via CCK-A and -B receptors was gained when either of the two receptor blockers was tested in rats subjected to the saline infusion alone. Here, the protein synthesis was decreased by 22% in the presence of the CCK-A receptor blocker and by 17% in the presence of the CCK-B receptor blocker. Interestingly, the effect of the two types of CCK receptor antagonists was not additive because when they were given at the same time the protein synthesis decreased by only 20%. The dependence of the pentagastrin-evoked response on the CCK receptors was confirmed, when not only the pentagastrin-treated animals but also the saline-treated animals were given the CCK receptor antagonists, and no increase in protein synthesis in the pentagastrin-treated animals was observed. In the rat parotid gland, activation of ß-adrenoceptors by intermittent stimulation of the sympathetic innervation (50 Hz, 1 s every tenth second for 30 min) or isoprenaline infusion (20 µg kg–1 min–1 for 30 min) causes an increase in the rate of protein synthesis, by 190 and 80%, respectively, that is mostly (110 versus 190%) or almost completely (70 versus 80%) dependent on NO generation (Sayardoust & Ekström, 2004). Although most probably of parenchymal origin, the ß-adrenoceptor-mediated generation of NO results from the activity of NO synthase of the neuronal type (Sayardoust & Ekström, 2003, 2004). The increase (175%) in parotid protein synthesis evoked by parasympathetic nerve stimulation (10 Hz for 30 min) seems to be independent of NO generation (Sayardoust & Ekström, 2006). In the present study, the pentagastrin-evoked response involved mobilization of NO. The magnitude of the decrease in protein synthesis when using the neuronal type of NO synthase blocker N-PLA was the same (23%) as when using the non-selective blocker L-NAME, so that not only neuronal NO synthase but also endothelial NO synthase and inducible NO synthase were inhibited. In contrast to the reduced protein synthesis in response to either of the two types of CCK receptor blockers or the combination of the two presently observed, L-NAME caused no reduction in protein synthesis in animals treated with saline alone. Also, in a previous study, the parotid protein synthesis in the anaesthetized rat under ‘basal’ conditions was unaffected by NO synthase inhibitors (Sayardoust & Ekström, 2004). The results suggest that the CCK-A and -B receptor-mediated synthesis of parotid protein results from mobilization of both non-NO-dependent and NO-dependent mechanisms, as is the case for the ß-adrenoceptor-mediated increase in protein synthesis resulting from stimulation of the sympathetic innervation (Sayardoust & Ekström, 2004). Furthermore, the results suggest that strong rather than weak stimuli of the CCK receptors activates neuronal type NO synthase to generate NO. Thus, the NO-dependent mechanism is likely to be activated not only by gastrin but also by cholecystokinin in response to a meal (Liddle et al. 1984; Qader et al. 2005), while fasting levels of these hormones or levels in between meals are likely to contribute to the maintenance of the non-NO-dependent protein synthesis.
Using the protocol of Sreebny et al. (1971), the glands were removed 15 min after the intravenous administration of [3H]leucine. By using such a short labelling time, all the radioactivity of the extracellular fluid is thought to be in the trichloroacetic acid-soluble fraction (Sreebny et al. 1971). Thus, the trichloroacetic acid-insoluble label of the parotid gland is not contaminated by serum components. This time period is also too short to allow radioactive trichloroacetic acid-insoluble material to be lost to the saliva. The fact that the animals in the present study were exsanguinated before removing the glands and that the removed glands were briefly dried on filter paper served as extra precautions to minimize contamination of the trichloroacetic acid-insoluble fraction.
Most of the protein synthesis of the rat parotid gland is directed towards producing secretory products (Sreebny et al. 1971). The synthesis of total cellular protein and amylase is thought to be a direct agonist effect temporally dissociated from and independent of the agonist-evoked secretory activity (Grand & Gross, 1969). This opinion gains support from the present finding of protein synthesis depending on both types of CCK receptors, combined with the earlier finding of protein secretion depending on only CCK-A receptors (Çevik Aras & Ekström, 2006). Agonists coupled to mobilization of cAMP (isoprenaline and vasoactive intestinal polypeptide) and Ca2+ (bethanechol) are associated with increases in parotid gland protein synthesis (Johnson & Sreebny, 1973; Ekström et al. 2000). The intracellular parotid signalling mechanisms of CCK-A and -B receptors are unknown. Apart from the classical intracellular pathways (Ca2+ and cAMP), other signalling pathways are also likely to be involved in regulating protein synthesis, as discussed for pancreatic acinar cells (Williams, 2001). Interestingly, our previous in vitro findings on protein secretion from rat parotid gland tissue suggest that the NO generation is associated with the cAMP pathway rather than with the Ca2+ pathway (Sayardoust & Ekström, 2003). Future studies should focus, among other things, on the phenomena behind the observation that the same types of receptors may activate both non-NO-dependent and NO-dependent mechanisms, as previously described for the ß-adreneoceptors (Sayardoust & Ekström, 2004) and presently for the CCK receptors.
The CCK receptor-mediated influence on parotid protein synthesis, presently observed, is probably associated with protein secretion rather than with hypertrophy or hyperplasia. Treatment with pentagastrin and CCK-8 over a period of time is without effect on the weight of the rat parotid gland (Månsson et al. 1990; Axelson et al. 1996). This is in contrast to the gain in pancreatic gland weight in rats subjected to prolonged treatment with pentagastrin or CCK-8 (Maystone & Barrowman, 1971; Månsson et al. 1990; Axelson et al. 1996). In isolated systems of pancreatic acinar cells, both types of CCK receptors may be involved in protein synthesis (Pradel et al. 1993; Desbois et al. 1999).
The pentagastrin-induced protein synthesis presently observed was small in comparison with the threefold increase in parotid protein synthesis in response to electrical stimulation of the parasympathetic or sympathetic innervation (Ekström et al. 2000; Sayardoust & Ekström, 2004, 2006). The relative pentagastrin-induced response was, however, larger when considering the parotid protein synthesis of rats in response to food intake, since in this case it was one-quarter of the response food intake (Ekström & Reinhold, 2001). Interestingly, in feeding experiments, a certain loss of glandular amylase activity (Ekström et al. 1993) and increase in protein synthesis (Ekström & Reinhold, 2001) persist in parasympathetically denervated parotid glands under muscarinic and adrenoceptor blockade. Although one explanation of these phenomena might be an action on the secretory cells of non-adrenergic, non-cholinergic transmitter mechanisms of nerves escaping the surgery (Ekström et al. 1988; Khosravani et al. 2006), there is also the possibility that gastrointestinal hormones, such as cholecystokinin and gastrin, contribute to the response of these denervated glands.
Although the present series of experiments on anaesthetized animals, using pentagastrin at a relatively high dose (Ballabeni et al. 2002), did not mimic physiological conditions, they provided reproducible data that indicate a possible action of cholecystokinin and gastrin under natural circumstances on both CCK-A and -B receptors, causing parotid protein synthesis via a non-NO-dependent mechanism at a low level of receptor activation and via a NO-dependent mechanism, through neuronal type NO synthase activity, at a high level of receptor stimulation. It should be mentioned that cholecystokinin may exist in autonomic nerves (Rehfeld, 2004). Whether this is the case in salivary glands is unknown. If present in salivary nerves, there may be a possibility that the CCK receptors of the parotid glands are not only under hormonal influence but also under neural influence.
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References |
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Ballabeni V, Calcina F, Bosetti M, Chiavarani M, Bertoni S, Impicciatore M & Barocelli E (2002). Different role of the histamine H3-receptor in vagal, betanechol-, pentagastrin-induced gastric acid secretion in anaesthetized rats. Scand J Gastroenterol 37, 754–758.
Çevik Aras H & Ekström J (2006). Cholecystokinin- and gastrin-induced protein and amylase secretion from the parotid gland of the anaesthetized rat. Regul Pept DOI: 10.1016/j.regpep.2006.01.004.
Desbois CLE, Huërou-Luron Dufresne M, Estival A, Clerc P, Romé V, Clemente F, Guilloteau P & Fourmy D (1999). The CCKB/gastrin receptor is coupled to the regulation of enzyme secretion, protein synthesis and p70, S6 kinase activity in acinar cells from ElasCCKB transgenic mice. Eur J Biochem 266, 1003–1010.
Ekström J, Ekman R, Håkanson R, Sjögren S & Sundler F (1988). Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P. Neuroscience 26, 933–949.
Ekström J, Engdal Havel G & Reinhold A-C (2000). Parasympathetic non-adrenergic, non-cholinergic-induced protein synthesis and mitogenic activity in rat parotid glands. Exp Physiol 85, 171–176.
Ekström J, Helander HF & Tobin G (1993). Parasympathetic non-adrenergic non-cholinergic mechanisms in reflex secretion of parotid acinar granules in conscious rats. J Physiol 472, 233–244.
Ekström J & Reinhold AC (2001). Reflex-elicited increases in female rat parotid protein synthesis involving parasympathetic non-adrenergic, non-cholinergic mechanisms. Exp Physiol 86, 605–610.
Grand RJ & Gross PR (1969). Independent stimulation of secretion and protein synthesis in rat parotid gland. The influence of epinephrine and dibutyryl cyclic adenosine 3',5'-monophosphate. J Biol Chem 244, 5608–5615.
Johnson D & Sreebny LM (1973). Effect of isoproterenol on synthesis and secretion in the rat parotid gland. Lab Invest 28, 263–269.
Khosravani N, Sandberg M & Ekström J (2006). The otic ganglion and its parotid connection in the rat: cholinergic pathways, reflex secretion and a secretory role for the facial nerve. Exp Physiol 91, 239–247.
Kitano M, Norlén P & Håkanson R (2000). Gastric submucousal microdialysis: a method to study gastrin- and food-evoked mobilization of ECL-cell histamine in conscious rats. Regul Pept 86, 113–123.
Liddle RA, Goldfine ID & Williams JA (1984). Bioassay of plasma cholecystokinin in rats: effects of food, trypsin inhibitor, and alcohol. Gastroenterology 87, 542–549.
Makovec F, Bani M, Cereda R, Chiste R, Pacini MA, Revel L, Rovati LA, Rovati LC & Setnikar I (1987). Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. Arzneimittelforschung 37, 1265–1268.
Makovec F, Revel L, Letari O, Mennuni L & Impicciatore M (1999). Characterization of antisecretory and antiulcer activity CR 2945, a new potent and selective gastrin/CCKB receptor antagonist. Eur J Pharmacol 369, 81–90.
Månsson B, Nilsson BO & Ekström J (1990). Effects of repeated infusions of substance P and vasoactive intestinal peptide on the weights of salivary glands subjected to atrophying influences in rats. Br J Pharmacol 101, 853–858.
Maystone PD & Barrowman JA (1971). The influence of chronic adminstration of pentagastrin on the rat pancreas. Q J Exp Physiol 56, 113–122.
Moncada S (1992). The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand 145, 201–227.
Pradel P, Estival A, Seva C, Wicker-Planquart C, Puigserver A, Vaysse N & Clemente F (1993). Caerulein and gastrin (2-17ds) regulate differently synthesis of secretory enzymes, mRNA levels and cell proliferation in pancreatic acinar cells (AR4-2J). Biochem J 290, 219–224.
Qader SS, Salehi A, Håkanson R, Lundquist I & Ekelund M (2005). Long-term infusion of nutrients (total parenteral nutrition) suppresses circulating ghrelin in food-deprived rats. Regul Pept 131, 82–88.
Rehfeld JF (2004). Cholecystokinin. Best Pract Clin Endocrin Metabol 18, 569–586.
Sayardoust S & Ekström J (2003). Nitric oxide-dependent in vitrosecretion of amylase from innervated or chronically denervated parotid glands of the rat in response to isoprenaline and vasoactive intestinal peptide. Exp Physiol 88, 381–387.
Sayardoust S & Ekström J (2004). Nitric oxide-dependent protein synthesis in parotid and submandiblular glands of anaesthetized rats upon sympathetic stimulation or isoprenaline administration. Exp Physiol 89, 219–227.
Sayardoust S & Ekström J (2006). Parasympathetic nerve-evoked protein synthesis, mitotic activity and salivary secretion in the rat parotid gland and the dependence on NO-generation. Arch Oral Biol 51, 189–197.
Sreebny LM, Johnson DA & Robinovitch MR (1971). Functional regulation of protein synthesis in the rat parotid gland. J Biol Chem 246, 3879–3884.
Williams JA (2001). Intracellular signal mechanisms activated by cholecystokinin-regulating synthesis and secretion of digestive enzymes in pancreatic acinar cells. Annu Rev Physiol 63, 77–97.
Zhang
HQ, Fast
W, Marletta
MA, Martasek
P
&
Silvermann
RB (1997). Potent and selective inhibition of neuronal nitric oxide synthase by N-propyl-L-arginine. J Med Chem
40, 3869–3870.
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