Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: Role of GABAA and GABAC receptors
2007; Elsevier BV; Volume: 52; Issue: 8 Linguagem: Inglês
10.1016/j.neuropharm.2007.03.016
ISSN1873-7064
AutoresMaria Grazia Zizzo, Flavia Mulè, Rosa Serio,
Tópico(s)Ion Channels and Receptors
ResumoWe investigated, in vitro, the effects of γ-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABAA-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABAC-receptor antagonist and it was not affected by phaclofen, a GABAB-receptor antagonist. Muscimol, GABAA receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABAC receptor agonist, induced an inhibitory effect, consisting in the reduction of the amplitude of the spontaneous contractions and muscular relaxation, which was antagonised by TPMPA, GABAC-receptor antagonist, TTX or Nω-nitro-l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not affected by hexamethonium. In conclusion, our study indicates that GABA is a modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA may act through neuronal presynaptic receptors, namely GABAA receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABAC receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.
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