gamma-Aminobutyric acid-A receptor-mediated suppression of 5-hydroxytryptamine-induced guinea-pig basilar artery smooth muscle contractility.
The mechanism of gamma-aminobutyric acid (GABA)-induced suppression of 5-hydroxytryptamine (5HT)-induced contractility of cerebral blood vessels was studied in single smooth muscle cells isolated from the guinea-pig basilar artery. GABA reduced 5HT-induced contraction of single smooth muscle cells, and the effect of GABA was mimicked by muscimol, but not baclofen. The response of muscimol was antagonized by bicuculline, thereby indicating that GABAA receptors exist on the smooth muscle of the basilar artery. Since GABA did not change the contraction induced by the addition of Ca2+ to the Ca2+-free medium in the presence of high K+, it is unlikely that GABA inhibits the influx of extracellular Ca2+. The caffeine-induced contraction in the Ca2+-free medium was reduced by GABA, and the effect of GABA was not obtained by treatment with furosemide and in the Cl- -free medium. These results indicate that GABA acts on the GABAA receptor located on smooth muscle cells and reduces the contractility of the basilar artery by suppression of the mobilization of intracellular Ca2+.
Shirakawa
J
J
Department of Pharmacology, Kobe University School of Medicine, Japan.
Hosoda
K
K
Taniyama
K
K
Matsumoto
S
S
Tanaka
C
C
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D012701:Serotonin; D002110:Caffeine; D005680:gamma-Aminobutyric Acid; D011188:Potassium