Original Article

Involvement of a putative G-protein-coupled receptor and a branching pathway in argipressin (4-8) signal transduction in rat hippocampus

Authors: Li-Ya Qiao, Yu-Cang Du

Abstract

AIM: To study the signal transduction pathway induced by argipressin (4-8) (AVP4-8) in rat hippocampus.
METHODS: Rat hippocampi were sectioned transversely at 300 microns with a tissue chopper and transferred to fresh incubation solution circulated with a humidified gas mixture of 95% O2 + 5% CO2 at 36 +/- 0.5 degrees C. After incubation with various drugs, MAP kinase (MAPK) activity and Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation were measured. RESULTS: The main findings are: (1) The AVP4-8-stimulated MAPK activity and the CaMKII autophosphorylation were blocked by ZDC(C)PR, an antagonist of AVP4-8, and also completely inhibited by pertussis toxin, a selective inhibitor of the G-protein-coupled receptor (GPCR). But, AVP-induced MAPK activation was not sensitive to ZDC(C)PR or PTX. (2) Polymyxin B (PMB), an inhibitor of protein kinase C (PKC), markedly suppressed the peptide-activation of MAPK, but did not affect CaMKII autophosphorylation. Phorbol myristate acetate (TPA), an activator of PKC, elicited an increase of MAPK activity, but did not further influence the level of AVP4-8-enhanced MAPK activity; Nevertheless, the extent of CaMKII activation was attenuated by TPA. (3) The enhancement of MAPK activity was not reduced by KN-62, a specific inhibitor of CaMKII. (4) AVP4-8 did not show any influence on cAMP production.
CONCLUSION: AVP4-8 stimulated signal transduction via a GPCR and a branching pathway in rat hippocampus.
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