Brain Research, 185 (1980) 51-57 51 © Elsevier/North-Holland Biomedical Press GABA RECEPTORS IN BOVINE CEREBRAL BLOOD VESSELS: BINDING STUDIES WITH [aH]MUSCIMOL DIANA N. KRAUSE,ESTHER WONG, PHYLLISDEGENER and EUGENE ROBERTS Division of Neurosciences, City of Hope National Medical Center, Duarte, Calif. 91010 (U.S.A.) (AcceptedAugust2nd, 1979) SUMMARY [3H]Muscimol, a potent GABA agonist used to label GABA receptor sites in brain and invertebrate striated muscle, was found to bind specifically to sites in a crude membrane fraction prepared from bovine cerebral blood vessels. Specific [3H]musci- mol binding was saturable of high affinity (Ka = 41 nM), and was selectively inhibited by GABA, specific GABA agonists, and the antagonist bicuculline with potencies similar to what has been found for GABA receptors in mammalian brain. GABA and several GABA agonists including muscimol have been reported to dilate isolated cerebral arteries, but not peripheral blood vessels. The pharmacology of the [3H]muscimol binding site correlated well with that of the vasodilatory response. No significant specific [3H]muscimol binding was detected in aorta and mesenteric arteries. The characteristics of the cerebrovascular muscimol binding site thus are indicative of a physiologically relevant GABA receptor associated with cerebral blood vessels. These findings suggest a direct role for GABA in cerebral vascular function. INTRODUCTION Studies with isolated cerebral arteries3, 5 suggested that 7-aminobutyric acid (GABA) may have a direct action on the cerebral vascular system in addition to its known inhibitory neurotransmitter effects on nerve cells and invertebrate striated musclelL GABA dilated segments of dog or cat basilar and middle cerebral arteries in vitro. This vasodilatory effect was dose-dependent, mimicked by known GABA agonists, and specifically blocked by the GABA antagonists picrotoxin and bicuculline but not by adrenoceptor and ganglion blocking agents, atropine, reserpine, tetro- dotoxin or ouabainZ, 5. These findings suggested the existence of specific cerebro- vascular GABA receptors. The present study was designed to identify such receptors biochemically by assaying for direct binding of a radioactive receptor ligand to the