Neuroregulation by vasoactive intestinal peptide (VIP) of mucus secretion in ferret trachea: activation of BKCa channels and inhibition of neurotransmitter release

摘要

class="enumerated" style="list-style-type:decimal">The aims of this study were to determine: (1) whether vasoactive intestinal peptide (VIP) regulates cholinergic and ‘sensory-efferent' (tachykininergic) ³⁵SO4 labelled mucus output in ferret trachea in vitro, using a VIP antibody, (2) the class of potassium (K⁺) channel involved in VIP-regulation of cholinergic neural secretion using glibenclamide (an ATP-sensitive K⁺ (KATP) channel inhibitor), iberiotoxin (a large conductance calcium activated K⁺ (BKca) channel blocker), and apamin (a small conductance Kca (SKca) channel blocker), and (3) the effect of VIP on cholinergic neurotransmission using [³H]-choline overflow as a marker for acetylcholine (ACh) release.Exogenous VIP (1 and 10 μM) alone increased ³⁵SO4 output by up to 53% above baseline, but suppressed (by up to 80% at 1 μM) cholinergic and tachykininergic neural secretion without altering secretion induced by ACh or substance P (1 μM each). Endogenous VIP accounted for the minor increase in non-adrenergic, non-cholinergic (NANC), non-tachykininergic neural secretion, which was compatible with the secretory response of exogenous VIP.Iberiotoxin (3 μM), but not apamin (1 μM) or glibenclamide (0.1 μM), reversed the inhibition by VIP (10 nM) of cholinergic neural secretion.Both endogenous VIP (by use of the VIP antibody; 1 : 500 dilution) and exogenous VIP (0.1 μM), the latter by 34%, inhibited ACh release from cholinergic nerve terminals and this suppression was completely reversed by iberiotoxin (0.1 μM).We conclude that, in ferret trachea in vitro, endogenous VIP has dual activity whereby its small direct stimulatory action on mucus secretion is secondary to its marked regulation of cholinergic and tachykininergic neurogenic mucus secretion. Regulation is via inhibition of neurotransmitter release, consequent upon opening of BKCa channels. In the context of neurogenic mucus secretion, we propose that VIP joins NO as a neurotransmitter of i-NANC nerves in ferret trachea.