Voltage-gated calcium channels involved in the inhibitory motor responses and vasoactive intestinal polypeptide release in the rat gastric fundus.
Ca(2+) inflow responsible for neurotransmitter release at most peripheral junctions is mainly mediated by activation of Ca(V)2.2 and Ca(V)2.1 channels. The aim of the present study was to characterize the voltage-gated Ca(2+) channels (VGCCs) responsible for the non-adrenergic non-cholinergic (NANC) relaxation and vasoactive intestinal polypeptide (VIP)-like immunoreactivity release in the rat gastric fundus. Precontracted longitudinal muscle strips of the rat gastric fundus were subjected to electrical field stimulation (EFS) under NANC conditions to evoke the relaxation and VIP-like immunoreactivity release. Nifedipine (1microM) completely relaxed the preparations, so that its effects on EFS-induced NANC relaxations could not be investigated. omega-Conotoxin GVIA (0.3-100nM) concentration-dependently reduced the amplitude of low frequency and the area under the curve (AUC) of high-frequency EFS-evoked relaxations (maximal reductions: approximately 55% and 42% of controls, respectively). The omega-conotoxin GVIA-resistant component of relaxation was not affected by omega-agatoxin IVA (300nM), omega-conotoxin MVIIC (100nM), SNX-482 (100nM) or flunarizine (1microM). omega-Conotoxin GVIA (30nM), omega-agatoxin IVA (30nM) and omega-conotoxin MVIIC (100nM) reduced high-frequency EFS-evoked VIP-like immunoreactivity release by approximately 70%, 27% and 35% of controls, respectively. omega-Conotoxin GVIA (30nM) plus omega-conotoxin MVIIC (100nM) almost abolished the EFS-induced VIP-like immunoreactivity outflow. In the rat gastric fundus, the activation of Ca(V)2.2 and P-type of Ca(V)2.1 channels is responsible for the EFS-induced VIP-like immunoreactivity release. In contrast, Ca(V)1 channels, novel VGCCs and/or molecular variants of VGCCs cloned to date may mediate a substantial component of the NANC relaxation.
Currò
Diego
D
Institute of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito, Rome, Italy. dcurro@rm.unicatt.it
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*; D020866:omega-Conotoxin GVIA / Q000633:toxicity*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014660:Vasoactive Intestinal Peptide; D020866:omega-Conotoxin GVIA