Facilitatory and inhibitory effects of gamma-aminobutyric acid on ganglionic transmission in the sympathetic cardiac nerves of the dog.

Effects of gamma-aminobutyric acid (GABA) on ganglionic transmission in the peripheral course of the sympathetic cardiac nerves were investigated in vagotomized and cardiac decentralized open-chest dogs. GABA (1-300 microgram/kg) was given i.v. during electrical stimulation of pre-or postganglionic fibers which induced a sustained acceleration of sinus rate. GABA in small doses of 1 and 3 microgram/kg augmented the sinus acceleration during electrical stimulation of the ansa subclavia which largely consists of preganglionic fibers, but depressed the sinus acceleration in large doses over 30 microgram/kg. With a dose of a 10 microgram/kg, its effect was dual and varied from preparation to preparation. On the other hand, GABA did not modify basal heart rate or the increase in heart rate in response to stimulation of the stellate cardiac nerve postganglionic fibers. These results clearly demonstrated dual effects of GABA on ganglionic transmission, i.e., facilitation in small doses and depression in large doses. The depression caused by large doses of GABA was markedly reduced by picrotoxin, 1 mg/kg, while the facilitation remained unaffected. Treatment with atropine, 1 mg/kg, and phenozy-benzamine, 1 mg/kg, failed to influence the effects of GABA. The possible mechanisms for these effects of GABA are discussed.