Modulation of the GABA shunt based on the knowledge of the enzymes involved

Abstract

A role for GABA in cerebral vascular function is supported by data indicating that specific GABA receptors and GABA-related enzymes are associated with cerebral blood vessels. 3H-Muscimol, which labels GABA receptor sites in brain, was found to bind to a crude membrane fraction prepared from pial blood vessels. Specific 3H-muscimol binding was saturable, of high affinity (KD = 41 nM), and was selectively inhibited by known GABA agonists. The relative potencies for the agonists in competing for the GABA binding site correlated well with the effectiveness of these compounds in dilating pial arteries in vitro (see Edvinsson et al., this volume). No specific 3H-muscimol binding was detected in aorta and mesenteric arteries. An association of GABA with cerebral blood vessels is further indicated by the presence of the enzyme which synthesizes GABA, glutamate decarboxylase (GAD) in pial arteries and intraparenchymal microvessels. GABA transaminase (GABA-T), the degradative enzyme for GABA, also has been demonstrated histochemically in large concentrations around brain vessels, but not around other, e.g. kidney, vessels. It is suggested that the GABA system in cerebral blood vessels is involved in the control of cerebral vascular tone.