Influence of GABA and ethylenediamine in the guinea-pig duodenum.
1. GABA induced concentration-dependent transient contractions of the guinea-pig duodenum, but only occasionally evoked small relaxatory responses. The GABA-induced contractions were blocked by atropine and tetrodotoxin but were not influenced by hexamethonium; during electrically evoked twitch contractions, GABA had a concentration-dependent inhibitory effect. 2. The concentration-response curve for the contractile effect of GABA was shifted to the right in a dose-dependent manner by bicuculline and picrotoxin, with a clear reduction of the maximal effect in the presence of picrotoxin. 3. Homotaurine and delta-aminovaleric acid but not baclofen mimicked the GABA-induced contractions; the responses induced by these GABAA receptor agonists were antagonized by atropine, tetrodotoxin and bicuculline. Baclofen concentration-dependently inhibited electrically evoked twitch contractions. 4. Ethylenediamine also had a GABA-like effect, and cross-desensitization developed between GABA and ethylenediamine. 5. The ethylenediamine-induced contractions were not antagonized by thiosemicarbazide; they were reduced by 3-mercaptopropionic acid but the GABA-induced contractions were reduced to the same extent. 6. It is concluded that GABA induces contraction of the guinea-pig duodenum by excitation of GABAA receptors on postganglionic cholinergic neurones; a GABAB receptor-mediated inhibitory effect can be observed during electrically evoked twitch contractions. Ethylenediamine mimicks the GABAA receptor-mediated effect probably by a direct effect on the GABAA receptors.
Barbier
A J
AJ
Heymans Institute of Pharmacology, University of Gent Medical School, Belgium.
Guenaneche
F
F
Lefebvre
R A
RA
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects; D004558:Electric Stimulation; D005029:Ethylenediamines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D015097:3-Mercaptopropionic Acid; D001640:Bicuculline; D005029:Ethylenediamines; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013654:Taurine; D013882:Thiosemicarbazones; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate