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

Abstract

In the isolated basilar artery of the rabbit, γ‐aminobutyric acid (GABA) (ED50±s.e.mean, 2.4 ± 1.1 × 10−5 m) produced a relaxation, if the tone had been increased with 5‐hydroxytryptamine (5‐HT). 3‐Aminoproprane sulphonic acid (3‐APS) produced a similar, but smaller relaxation, while baclofen had no effect. The relaxation produced by GABA was inhibited by bicuculline. Transmural electrical stimulation produced a reproducible contraction of the isolated basilar artery. In 9 out of 14 preparations GABA (ED50± s.e.mean, 5.6 ± 2.1 × 10−7 m) caused a reduction of the response, with a maximum of 49.2 ±4.3%. Bicuculline did not inhibit these responses to GABA. Baclofen (ED50±s.e.mean, 6.8± 1.4 × 10−7 m) produced a similar inhibition (47.4±3.2% maximum) but 3‐APS had no effect. GABA (10−4 m) had no effect on the tone of isolated mesenteric or internal carotid arteries from the rabbit, whether or not the tone was increased with 5‐HT. Similarly, GABA (10−4 m) did not produce any change in the responses to transmural stimulation in isolated mesenteric or internal carotid arteries. These findings are consistent with the presence of two types of GABA receptor on the rabbit basilar artery.

Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes

“…So far receptors with GABAB characteristics have been described in intestinal muscle (Kaplita, Waters & Triggle, 1982), atria vas deferens Stone, 1981), vascular muscle (Starke & Weitzell, 1981) and anoccocygeus muscle (Hughes, Mor- & Stone, 1982;Muyhaddin, Roberts & Woodruff, 1982a). They have also been demonstrated in the basilar artery (Anwar & Mason, 1982). In all cases the indications are that the receptor is located on nerve terminal inputs to the tissues.…”

Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation

“…22,24,25 Therefore, we tested the effect of GABA and the GABA A receptor inhibitor flumazenil on aortic rings. Increasing doses of GABA did not induce vasodilation (data not shown).…”

“…Because GABA A receptors have been involved in BDZ-induced vasodilation in different vascular beds 22,25 and because immunohistochemical studies showed the presence of a non-neuronal GABA A receptor in endothelial cells, 28 we tested the potential role of the GABA A receptor in midazolam-induced vasodilation. Our results exclude both the hypothesis that GABA A receptor mediates midazolam-induced vasodilation and that GABA A receptor can be potentially involved in mouse aorta vasodilation.…”

“…22 Aortic rings precontracted with KCl were treated either with increasing doses of GABA (dose-response curve from 10 À9 to 10 À4 mol l À1 , Sigma) or, after incubation with the central-type BDZ receptor antagonist flumazenil (1 mmol l À1 for 10 min), with midazolam (10 or 50 mmol l À1 ). We evaluated whether midazolam and GABA have a synergistic effect on vasodilation of the aortic rings by incubating KCl-precontracted rings with GABA (100 mmol l À1 for 10 min) before midazolam treatment.…”

Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia

“…The 'depressive' effects of GABA on cardiovascular function have been described in a number of studies (Takahashi et al, 1955;1959;Elliott & Hobbiger, 1959;Stanton, 1963;Vemulapalli & Barletta, 1984;Maggi et al, 1985a) and may be ascribed to: (a) interference with transmission in sympathetic ganglia (Kato & Kuba, 1980;Kushiku & Furukawa, 1985;Maggi et al, 1985c,d) and/or (b) a prejunctional inhibition of transmitter release from sympathetic nerve endings (Starke & Weitzell, 1980;Bowery et al, 1981;Anwar & Mason, 1982;Muhyaddin et al, 1983;Manzini et al, 1985). It is quite possible that the 'depressive' effects of GABA observed in the present study depend upon a transient blunting ofsympathetic control on cardiovascular function since the amplitude of 'depressive' changes induced by GABA was proportional to resting values of cardiovascular parameters.…”