Voltage-gated calcium channels involved in the inhibitory motor responses and vasoactive intestinal polypeptide release in the rat gastric fundus

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Abstract

Ca2+ inflow responsible for neurotransmitter release at most peripheral junctions is mainly mediated by activation of CaV2.2 and CaV2.1 channels. The aimof the present studywas to characterize the voltage-gated Ca2+ 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 funduswere subjected to electrical field stimulation (EFS) under NANC conditions to evoke the relaxation and VIP-like immunoreactivity release. Nifedipine (1 μM) completely relaxed the preparations, so that its effects on EFS-induced NANC relaxations could not be investigated. ω-Conotoxin GVIA (0.3–100 nM) concentration-dependently reduced the amplitude of lowfrequency and the area under the curve (AUC) of high-frequency EFS-evoked relaxations (maximal reductions: approximately 55% and 42% of controls, respectively). The ω-conotoxin GVIA-resistant component of relaxation was not affected by ω-agatoxin IVA (300 nM), ω-conotoxin MVIIC (100 nM), SNX-482 (100 nM) or flunarizine (1 μM). ω-Conotoxin GVIA (30 nM), ω-agatoxin IVA (30 nM) and ω-conotoxin MVIIC (100 nM) reduced high-frequency EFS-evoked VIP-like immunoreactivity release by approximately 70%, 27% and 35% of controls, respectively. ω-Conotoxin GVIA (30 nM) plus ω-conotoxin MVIIC (100 nM) almost abolished the EFS-induced VIP-like immunoreactivity outflow. In the rat gastric fundus, the activation of CaV2.2 and P-type of CaV2.1 channels is responsible for the EFSinduced VIP-like immunoreactivity release. In contrast, CaV1 channels, novel VGCCs and/or molecular variants of VGCCs cloned to date may mediate a substantial component of the NANC relaxation.
Lingua originaleEnglish
pagine (da-a)207-213
Numero di pagine7
RivistaEuropean Journal of Pharmacology
Volume628
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Agatoxin
  • Conotoxin
  • NANC (non-adrenergic non-cholinergic) relaxation
  • Rat gastric fundus
  • VGCCs (voltage-gated calcium channels)
  • VIP (vasoactive intestinal polypeptide) release

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