Cholinergic contractions induced by GABA-A receptor activation in the guinea-pig ileum are inhibited by alpha-chymotrypsin and potentiated by diazepam.
The influence of alpha-chymotrypsin and diazepam on the phasic (mainly direct) and tonic (indirect, probably substance P-mediated) components of intestinal cholinergic contractions, induced by the GABA-A receptor agonist 3-aminopropane sulphonic acid (3-APS), was investigated in the guinea-pig ileum. alpha-Chymotrypsin, at a concentration (20 U/ml) not affecting submaximal Ach (0.1 microM) contractions, preferentially depressed the tonic component of the 3-APS (30 microM)-induced response. A brief exposure (10 or 60 sec) to diazepam (0.1 microM) potentiated both the phasic and the tonic contractions evoked by low (10, 30 microM) 3-APS concentrations. This potentiation was prevented by bicuculline (30 microM), hyoscine (1 microM) and flumazenil (1, 3 microM). These results provide further support for an involvement of a peptide neurotransmitter on GABA-A receptor-mediated cholinergic response in the ileum. The modulation of this response by diazepam is probably exerted through recognition sites resembling the "central type" benzodiazepine receptors.
Tonini
M
M
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Onori
L
L
Manzo
L
L
Rizzi
C A
CA
Crema
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D011963:Receptors, GABA-A; D013654:Taurine; D005442:Flumazenil; C001355:tramiprosate; D002918:Chymotrypsin; D000109:Acetylcholine; D003975:Diazepam; D002211:Capsaicin; D001640:Bicuculline