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Vasoactive intestinal polypeptide modulates GABAA receptor function through activation of cyclic AMP

Published online by Cambridge University Press:  02 June 2009

Margaret L. Veruki
Affiliation:
Graduate Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester
Hermes H. Yeh
Affiliation:
Graduate Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester Bowman Gray School of Medicine, Wake Forest University, Winston-Salem

Abstract

Vasoactive intestinal polypeptide (VIP) has been shown to potentiate current responses elicited by activation of the GABAA receptor (IGABA) in freshly dissociated ganglion cells of the rat retina. Here we tested the hypothesis that this heteroreceptor cross talk is mediated by an intracellular cascade of events that includes the sequential activation of a stimulatory guanine nucleotide binding (Gs) protein and adenylate cyclase, the subsequent increase in levels of cyclic AMP and, finally, the action of the cyclic AMP-dependent protein kinase (PKA). Intracellular dialysis of freshly dissociated ganglion cells with GTPγs irreversibly potentiated IGABA, while GDPßs either decreased or had no effect on IGABA. Additionally, GDPßs blocked the potentiation of IGABA by VIP. Cholera toxin rendered VIP ineffective in potentiating IGABA, while pertussis toxin had no effect on the VIP-induced potentiation of IGABA. Extracellular application of either forskolin or 8-bromo-cyclic AMP potentiated IGABA, as did the introduction of cyclic AMP directly into the intracellular compartment through the recording pipet. Intracellular application of cyclic AMP-dependent protein kinase (PKA) potentiated IGABA, while a PKA inhibitor blocked the potentiating effect of VIP. These results lead us to conclude that activation of a cyclic AMP-dependent second-messenger system mediates the modulation of GABAA receptor function by VIP in retinal ganglion cells.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 1994

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