Γ‐aminobutyric Acid and Postganglionic Sympathetic Transmission in the Pulmonary Artery of the Rabbit

Abstract

1 The effect of gamma-aminobutyric acid (GABA) on postganglionic sympathetic neurotransmission was studied in strips of the rabbit pulmonary artery. The strips were preincubated with 3H-noradrenaline and then superfused with 3H-amine-free medium. They were stimulated either electrically at 2 Hz, or by 60 mM potassium, or by 1 microM tyramine. 2 GABA (1 - 1000 microM) did not change the basal outflow of tritium, but decreased the electrically evoked overflow as well as the contractile response. GABA 1 microM decreased the evoked overflow by 12%, and GABA 1000 microM, by 42%. The effect of GABA was not changed by yohimbine, propranolol, cocaine, corticosterone, or indomethacin. It was not antagonized by picrotoxin or bicuculline methiodide. GABA 100 microM also slightly reduced the potassium-evoked overflow of tritium but did not change the tyramine-evoked overflow. 3 The results show that, in the pulmonary artery of the rabbit, GABA inhibits the release of noradrenaline. Its effect is independent of alpha- and beta-adrenoreceptors and is not mediated by prostaglandins. The effect may be due to activation of presynaptic receptors which appear to differ from conventional GABA receptors inasmuch as they are insensitive to blockade by either picrotoxin or bicuculline.

Effects of GABA on noradrenaline release and vasoconstriction induced by renal nerve stimulation in isolated perfused rat kidney

“…Our present results suggest that GABA interferes with neural NA release and thereby attenuates vasoconstriction during activation of sympathetic nervous system in the kidney. It has been reported previously that GABA can suppress peripheral adrenergic neurotransmission in several kinds of vasculature such as the isolated goat cerebral artery (Miranda et al, 1989), rabbit pulmonary artery (Starke & Weitzell, 1980) and rabbit ear artery (Manzini et al, 1985). The present study is the ®rst to demonstrate an inhibitory role of GABA in neurotransmission of the renal vasculature.…”

“…GABA releases catecholamines from the isolated perfused adrenal medulla via GABA A receptors (Gonza lez et al, 1992), suggesting that GABAergic mechanisms are involved in the regulation of adrenal medullary function. On the other hand, GABA has been reported to aect sympathetic neurotransmission by acting on presynaptic GABA B receptors in the rabbit pulmonary artery (Starke & Weitzell, 1980), the rabbit ear artery (Manzini et al, 1985) and the bovine ovarian follicle (Kannist et al, 1986). Binding sites for GABA A receptors (Amenta et al, 1988) and GABA B receptors (ErdoÈ , 1990) have been con®rmed to exist in the rat kidney.…”

Involvement of γ-Aminobutyric Acid (GABA) B Receptors in the Hypotensive Effect of Systemically Administered GABA in Spontaneously Hypertensive Rats

“…Furthermore, results from in vivo studies apparently contradict those from in vitro work regarding the type of GABA receptor involved. Namely, GABA A receptor antagonists (e.g., picrotoxin, bicuculline) reduced the hypotensive action of intravenous GABA (16, 19 -21), whereas the GABAB antagonist 2-hydroxysaclofen (but not a GABA A -receptor antagonist) counteracted the vasodilatory action of GABA in experiments using isolated pulmonary (22), renal (23), or mesenteric (24) arteries. Therefore, we designed our investigation first to clarify the minimum effective intraduodenal dose of GABA to confirm whether a low dose of oral GABA has real potential to cause a hypotensive effect.…”

Two Actions of Γ‐aminobutyric Acid on the Responses of the Isolated Basilar Artery From the Rabbit

“…In our experiments using peripheral vessels no evidence could be obtained for a similar presynaptic receptor, but Starke & Weitzell (1980) have found evidence of inhibition of transmitter release and contractions by GABA using the pulmonary artery from the rabbit. The response only appeared at 10-6 M; and 10-3 M was required to produce a maximal effect, suggesting that the receptors involved were different.…”