Neuropeptide Y (NPY) is a 36-amino-acid polypeptide that exerts its biological action through Gi/Go-protein coupled receptors in the central and peripheral nervous systems. It has been demonstrated to have potent depressor effect in the nucleus tractus solitarii (NTS) of rats, and activation of both NPY Y1 and Y2 receptors would phosphorylate ERK in CHO K1 cell. Brain stem nuclei such as nucleus of tractus solitari (NTS) and rostral ventrolateral medulla (RVLM) are innervated by neurons capable of synthesizing nitric oxide (NO), and inhibition of NO synthesis in these areas cause sustained hypertension and decrease baroreceptor sensitivity. Our previous studies already suggested that NO produced in the braistem nuclei play an important role in cardiovascular regulation. It was shown that NPY induces vasodilation of human subcutaneous arteries by a NO dependent pathway. In the present study, we investigated the molecular signaling mechanisms involved in NPY-induced cardiovascular modulation in NTS. Unilateral microinjection of NPY into the NTS of WKY rats produced prominent depressor and bradycardic effects. Pretreatment with a selective non-peptide neuropeptide Y1 (NPY1) receptor antagonist BIBP3226; Gi/Go-protein inhibitor Pertussis toxin, MEK inhibitor PD98059, significant attenuated the cardiovascular response evoked by NPY. Western blot and immunohistochemistry studies showed NPY and NPY Y1 agonist [Leu31 Pro34] NPY increased ERK1/2 phosphorylation, and PD98059, BIBP3226 attenuated the NPY-induced phosphorylation significantly. Non-selcetive NOS inhibitor L-NAME and eNOS preferential inhibitor L-NIO significantly attenuated the cardiovascular response evoked by NPY, however nNOS preferential inhibitor 7-NI and nNOS specific inhibitor Vinyl-L-NIO did not cause any changes. Western blot and immunohistochemistry studies showed NPY increased eNOS phosphorylation, but not nNOS. Our results showed that NPY induced ERK1/2 phosphorylation through NPY Y1 receptor, and its downstream eNOS-NO pathway involved in NPY mediated cardiovascular effects.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0728106-193045 |
| Date | 28 July 2006 |
| Creators | Yang, Ya-Chun |
| Contributors | Ching-Jiunn Tseng, Pei-Jun Lu, Wen-Chun Hung, Hsiao, Michael |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0728106-193045 |
| Rights | not_available, Copyright information available at source archive |
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