Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: role of GABA(A) and GABA(C) receptors.
We investigated, in vitro, the effects of gamma-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 GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) 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, GABA(C)-receptor antagonist, TTX or N(omega)-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 GABA(A) receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABA(C) receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.
Zizzo
Maria Grazia
MG
Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Mulè
Flavia
F
Serio
Rosa
R
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003561:Cytarabine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004386:Duodenum / Q000166:cytology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009118:Muscimol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010721:Phosphinic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018079:Receptors, GABA / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D018755:GABA Agonists; D018756:GABA Antagonists; C087200:GABA-C receptor; D010721:Phosphinic Acids; D011725:Pyridines; D018079:Receptors, GABA; D018080:Receptors, GABA-B; D003561:Cytarabine; C055054:N(4)-chloroacetylcytosine arabinoside; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline