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VIP and PACAP potentiation of nicotinic ACh‐evoked currents in rat parasympathetic neurons is mediated by G‐protein activation
Author(s) -
Liu DongMei,
Cuevas Javier,
Adams David J.
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00116.x
Subject(s) - long term potentiation , vasoactive intestinal peptide , acetylcholine , medicine , endocrinology , chemistry , agonist , nicotinic agonist , patch clamp , pertussis toxin , acetylcholine receptor , muscarinic acetylcholine receptor , g protein , receptor , neuropeptide , biology
Abstract The effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP27 and PACAP38) on isolated parasympathetic neurons of rat intracardiac and submandibular ganglia were examined under voltage clamp using whole‐cell patch‐clamp recording techniques. VIP and PACAP (≤ 10 n m ) selectively and reversibly increased the affinity of nicotinic acetylcholine receptor channels (nAChRs) for their agonists resulting in a potentiation of acetylcholine (ACh)‐evoked whole‐cell currents at low agonist concentrations. VIP‐induced potentiation was observed with either ACh or nicotine as the cholinergic agonist. The VIP‐ but not the PACAP‐induced potentiation of ACh‐evoked currents was inhibited by [Ac‐Tyr 1 , D‐Phe 2 ]‐GRF 1–29, amide (100 n m ), a selective antagonist of VPAC 1 and VPAC 2 receptors; whereas the PACAP38‐ but not the VIP‐induced potentiation was inhibited by 100 n m PACAP6–38, a PAC 1 and VPAC 2 receptor antagonist. The signal transduction pathway mediating VIP‐ and PACAP‐induced potentiation of nicotinic ACh‐evoked currents involves a pertussis toxin (PTX)‐sensitive G‐protein. Intracellular application of 200 μ m GTPγS or GDPβS inhibited VIP‐induced potentiation of ACh‐evoked whole‐cell currents. GTPγS alone potentiated ACh‐ and nicotine‐evoked currents and the magnitude of these currents was not further increased by VIP or PACAP. The G‐protein subtype modulating the neuronal nAChRs was examined by intracellular dialysis with antibodies directed against α o , α i‐1,2 , α i‐3 or β G‐protein subunits. Only the anti‐Gα o and anti‐Gβ antibodies significantly inhibited the effect of VIP and PACAP on ACh‐evoked currents. The potentiation of ACh‐evoked currents by VIP and PACAP may be mediated by a membrane‐delimited signal transduction cascade involving the PTX‐sensitive G o protein.