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gamma-Aminobutyric acid (GABA) produced a biphasic action, that is, a relaxation followed by a contraction in the isolated dog basilar artery. Repeated applications of each concentration of GABA (10(-6), 10(-5), 10(-4), 10(-3) M) at regular intervals under resting conditions caused a stepwise increase in the contractile response. Marked reproducible contractile responses occurred (ED50: 1.3 X 10(-5) M), after at least 8-10 applications. The GABA-induced contraction as well as relaxation was blocked by bicuculline and picrotoxin. Pretreatment with inhibitors of prostaglandin synthesis such as aspirin (3 X 10(-6) to 3 X 10(-4) M) and indomethacin (3 X 10(-6) M) reduced the contractile response to GABA in an irreversible manner and without affecting the relaxation induced by GABA. These inhibitors increased the resting tone but reduced the tone in strips subjected to repeated applications of GABA. 15-Hydroperoxyarachidonic acid at concentrations of 1 X 10(-6) and 1 X 10(-5) M also attenuated the contractile response to GABA in a dose-dependent fashion. These observations suggest that GABA may modulate the contractile effect by inducing the production of contraction-causing prostaglandin(s) mediated through GABA receptors and/or by some as yet undefined mechanism.
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