Modulation of Central Control of Hypotensive Effects by Neuropeptide Y is Mediated through RSK Induced Activation of Endothelial Nitric Oxide Synthase.
Summary of "Modulation of Central Control of Hypotensive Effects by Neuropeptide Y is Mediated through RSK Induced Activation of Endothelial Nitric Oxide Synthase."
Background and purpose: Neuropeptide Y (NPY) is a 36-amino-acid polypeptide found abundantly in the central and peripheral nervous system. It has been demonstrated that NPY exerts a potent depressor effect via the activation of both NPYY1 and NPYY2 receptors in the nucleus tractus solitarii (NTS) of rats. However, the precise mechanisms involved in NPY-mediated activity remained unclear. Experimental approach: Microinjection of NPY into the NTS of Wistar-Kyoto rats in the absence or presence of a selective non-peptide antagonist of the NPYY1 receptor, PKC inhibitor, PI3 kinase inhibitor, nitric oxide synthase (NOS) inhibitor, endothelial NOS (eNOS)-selective inhibitor, neuronal NOS (nNOS)-specific inhibitor or MAP kinase inhibitor, was used to determine the underlying mechanism of NPY-induced depressor effect in the NTS. Key results: Unilateral microinjection of exogenous NPY (4.65 pmol/60 nL) into the NTS of urethane-anesthetized Wistar-Kyoto rats resulted in a prominent decrease in blood pressure and heart rate. Microinjection of NPYY1 receptor antagonist BIBP3226 or Gi/Go-protein inhibitor pertussis toxin into the NTS attenuated NPY-induced hypotensive effects. An NPYY1 agonist significantly increased the expression of extracellular signal-regulated kinase (ERK)1/2, ribosomal protein S6 kinase (RSK) and the phosphorylation of eNOS. RSK was also found to bind directly to eNOS and induced its phosphorylation at Ser1177. However, pretreatment with an eNOS inhibitor, but not a nNOS inhibitor, attenuated NPY-induced depressor and bradycardic effects in the NTS. Conclusions and implications: Collectively, these results suggested that NPY induced depressor effects are mediated by activating NPYY1 receptor-PKC-ERK-RSK-eNOS and Ca(2+) -eNOS signaling pathways which are involved in the regulation of blood pressure in the NTS. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Affiliation
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Radiation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Institute of Clinical Medicine, National Che
Journal Details
This article was published in the following journal.
Name: British journal of pharmacology
ISSN: 1476-5381
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22708658
- DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.02077.x
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