Effect of gamma-aminobutyric acid on neurally mediated contraction of guinea pig trachealis smooth muscle.
To determine whether gamma-aminobutyric acid (GABA) affects the contractile properties of airway smooth muscle and, if so, what the mechanism of action is, the authors studied guinea pig tracheal rings under isometric conditions in vitro. GABA and related substances, baclofen and muscimol, had no effect on the resting tension but reversibly depressed contractions induced by electrical field stimulation in a dose-dependent fashion, IC50 values (mean +/- S.E.) being 5.6 +/- 1.4 X 10(-6) M, 6.8 +/- 0.9 X 10(-6) M and 8.5 +/- 1.5 X 10(-5) M, respectively. In contrast, GABA did not alter the response to exogenous acetylcholine or the nonadrenergic noncholinergic inhibitory component. Pretreatment of tissues with bicuculline antagonized the inhibitory effect of GABA as well as that of baclofen. This inhibitory effect was not modified by propranolol, phentolamine, hemicholinium-3 or naloxone, but it was blocked by the Cl channel blocker furosemide and by the substitution of external Cl. These results suggest that GABA decreases the contractile response of airway smooth muscle to cholinergic nerve stimulation by inhibiting the evoked release of acetylcholine and that this effect is exerted by activating Cl-dependent, bicuculline-sensitive GABA receptors.
Tamaoki
J
J
Department of Medicine, University of California, San Francisco.
Graf
P D
PD
Nadel
J A
JA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D006168:Guinea Pigs; D006426:Hemicholinium 3 / Q000494:pharmacology; D066298:In Vitro Techniques; D009118:Muscimol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D009118:Muscimol; D006426:Hemicholinium 3; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D005665:Furosemide; D011433:Propranolol; D001418:Baclofen; D000109:Acetylcholine; D010646:Phentolamine