Muscarinic cholinergic receptor sites in cerebral blood vessels.

Muscarinic cholinergic receptor sites in cerebral blood vessels were analyzed directly by using radioligand binding techniques with the specific muscarinic antagonist [3H]quinuclidinyl benzilate (QNB) as ligand. Specific binding of [3H]QNB to membrane preparations from isolated bovine pia-arachnoid vessels was found to be saturable, of high affinity (Kd = 5.4 X 10(-10) M) and selectively inhibited by muscarinic antagonists (atropine) and agonists (acetylcholine, carbachol and methacholine). Scatchard and Hill plot analyses of the data indicated one class of sites for the antagonists, but two independent classes of sites were revealed with the agonists. Interestingly, the high and low affinities of the agonist sites correlated with the concentrations of agonist which have been reported to produce dilation and contraction, respectively, of isolated pial artery segments. A substantial number of specific [3H]QNB binding sites also were measured in isolated bovine cerebral microvessels providing direct evidence for muscarinic receptors in intracerebral vessels. In contrast, specific [3H]QNB binding was barely detectable in mesenteric blood vessels. Choline acetyltransferase (ChAT) activity was measured in parallel with [3H]QNB binding. The relative distribution of choline acetyltransferase was correlated with that for the binding, with the highest values observed in the intracerebral microvessels. This suggests a functional innervation of the cerebrovascular muscarinic receptors.