Autoradiographic localization of dopamine receptors in rat cerebral blood vessels

Abstract

Combined in vitro radioreceptor binding and autoradiographic techniques were used to analyze the pharmacological profile and the anatomical localization of dopamine (DA) DA 1 and DA 2 receptor sites in the arteries and arterioles of the pial-arachnoid membrane in the rat. [ 3H]SCH 23390, used as a ligand of DA 1 receptors, was bound by sections of rat cerebral vessels in a manner consistent with the labeling of DA 1 receptors, with a value of 2.2 nM for the dissociation constant (K d) and of 68.4 fmol/mg protein for the density of binding sites (B max). The ligand was bound primarily by the medial layer of cerebral arteries. The density of silver grains developed after exposure of cerebral vessel sections to [ 3H]SCH 23390 was unchanged after chemical sympathectomy with 6-hydroxydopamine (6-OHDA) and was not significantly different in either the circle of Willis arteries or in the pial-arachnoid arteries and arterioles. [ 3H]Spiroperidol was used as ligand of DA 2 receptors in the presence of ketanserin to block the possible binding to 5-HT 2 receptors. [ 3H]Spiroperidol was bound by sections of rat cerebral vessels in a manner consistent with labeling of DA 2 receptors, with K d and B max values of 1.9 nM and 39.8 fmol/mg protein, respectively. The ligand was bound primarily by the adventitia and the adventitial-medial border as well as by the intimal layer of cerebral arteries. The accumulation of adventitial and adventitial-medial silver grains developed after exposure of cerebral vessels sections to [ 3H]spiroperidol did not occur in 6-OHDA-treated animals. In contrast, chemical sympathectomy was without effect on the density of intimal silver grains. The density of adventitial silver grains was higher in the anterior than in the posterior circle of Willis and pial-arachnoid arteries and arterioles, as well as in the pial-arachnoid arteries and arterioles than in circle of Willis arteries. These findings indicate the existence of both DA 1 and DA 2 receptor sites in the rat cerebrovascular tree.