Diazepam potentiates GABA-contraction in guinea-pig ileum.
Both GABA-receptors and benzodiazepine receptors have recently been described in the ileum. In this work we tested whether an interaction between diazepam and GABA-A- or GABA-B-mediated effects took place in guinea-pig ileum longitudinal muscle. We found that diazepam dose-dependently (10(-9) M-10(-6) M) potentiates the contractions caused by the activation of GABA-A receptor while it is ineffective at the same doses on GABA-B- mediated effects (relaxation and inhibition of twitch response). The drug "per se" does not affect the ileum. Diazepam potentiation is specific since this drug does not potentiate contractions caused by acetylcholine (10(-8) M), 5-HT (10(-7) M), histamine (10(-7) M), and electrical stimulation. Diazepam potentiating effect was not evident in the presence of bicuculline (10(-5) M) or hyoscine (2 X 10(-7) M). Ro 15-1788 (10(-5)M) and beta CCE (10(-5)M) antagonized diazepam potentiation of GABA contraction, while PK 11195 (10(-5) M) was ineffective. We conclude that diazepam modulates the effects evoked by stimulation of peripheral GABA-A receptors, while it is ineffective on GABA-B mediated effects.
Luzzi
S
S
Spagnesi
S
S
Franchi-Micheli
S
S
Rosi
E
E
Ciuffi
M
M
Zilletti
L
L
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004357:Drug Synergism; D004558:Electric Stimulation; D005442:Flumazenil; 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*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001570:Benzodiazepinones; D002243:Carbolines; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C024915:beta-carboline-3-carboxylic acid ethyl ester; D001418:Baclofen; D003975:Diazepam