Received January 7, 2008
Revised January 25, 2008
Accepted after revision March 3, 2008
Cardiovascular Control [210]
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Characterization of a Functional (Pro)renin Receptor in Brain Neurons
Zhiying Shan 1,
Adolfo E Cuadra 1,
Colin Sumners 1,
Mohan K Raizada 1*
1 University of Florida
* To whom correspondence should be addressed. E-mail: mraizada{at}phys.med.ufl.edu.
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Abstract |
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(Pro)renin receptor (PRR), the newest member of the renin-angiotensin system (RAS), is turning out to be an important player in the regulation of the cardiovascular system. It plays a pivotal role in activation of the local RAS and by stimulation of signaling pathways involved in proliferative and hypertrophic mechanisms. However, the role of PRR in the brain remains unknown. Thus, our objective in this study was to determine if a functional PRR is present in neurons within the brain. Neuronal co-cultures from the hypothalamus and brainstem areas of neonatal rat brain express PRR mRNA. PRR immunoreactivity was primarily localized on the neuronal cell soma and in discreet areas in the neurites. Treatment of neurons with renin, in the presence of 2 µM losartan, caused a time- and dose-dependent stimulation of phosphorylation of ERK1 (p44) and ERK2 (p42 )isoforms of MAP kinase. Optimal stimulation of 4 fold was observed within 2 min with 20 nM renin. Electrophysiological recordings showed that treatment of the neurons with renin, in the presence of 2 µM losartan, resulted in a steady and stable decrease in action potential frequency (APF). A 54% decrease in APF was observed within 5 min of treatment that was attenuated by coincubation with a PRR blocking peptide. These observations demonstrate that the PRR is present in neurons within the brain and its activation by renin initiates the MAP kinase signaling pathway and inhibition of neuronal activity.
Key Words:
Brain, Receptor, Renin
