ROLE OF GABA RECEPTORS IN THE BRONCHIAL RESPONSE - STUDIES IN SENSITIZED GUINEA-PIGS

Background gamma-Aminobutyric acid (GABA), an important inhibitory neu rotransmitter in the mammalian central nervous system, is also found i n peripheral tissues, including the lung. GABA has recently been shown to modulate the contraction of airway smooth muscle. Objective We stu died the effect of GABA on the contractile properties of tracheal smoo th muscle by measuring the tension of the trachea isolated from non-se nsitized and ovalbumin (OA)-sensitized guinea-pigs under isometric con ditions.Methods Guinea-pigs were sensitized by intraperitoneal doses o f OA to prepare a bronchial asthma model. Tracheal spiral rings were p repared from the OA-sensitized as well as normal, non-sensitized guine a-pigs. Using the tracheal preparations, the effects of GABA and GABAa and GABAb receptor agonists (muscimol and baclofen) and antagonists ( bicuculline and saclofen) on the basal tone of the trachea and on trac heal contraction induced by electrical field stimulation (EFS) were de termined. The effect of GABA on tracheal contraction induced by exogen ous acetylcholine was also studied. Results GABA and GABA agonists and antagonists had no effect on the basal tone of normal guinea-pig trac heae. Both GABAa and GABAb receptor agonists, as well as GABA, suppres sed EFS-induced contraction of normal guinea-pig tracheae in a reversi ble, dose-dependent manner. Moreover, this suppression was reserved to the control level by either GABAa and GABAb receptor antagonists. In tracheal spiral ring prepared from OA-sensitized guinea-pigs, GABA and baclofen caused a smaller reversible inhibition of EFS-induced contra ction than in normal tracheal spiral ring, while muscimol inhibited EF S-induced tracheal contraction to a similar extent to that observed in normal tracheae. GABA had no effect on the tracheal contractile respo nse to acetylcholine. Conclusion The results suggest that there may be a biological mechanism mediated by prejunctional GABAb receptors whic h attenuates cholinergic contraction of airway smooth muscle and that dysfunction of the receptors may underlie the airway obstruction in as thmatics.