Binding of α- and β-adrenergic ligands to cerebral cortical membranes: Effect of 6-hydroxydopamine treatment and relationship to the responsiveness of cyclic AMP-generating systems in two rat strains

Abstract

The binding of an α-adrenergic antagonist, WB 4101 and of a β-adrenergic antagonist, dihydroalprenolol, to cerebral cortical membranes fromo two rat strains, Sprague-Dawley and F-344, was examined after intraventricular administration of 6-hydroxydopamine. Cyclic AMP-generating systems in cerebral cortical slices from Sprague-Dawley rats respond to norepinephrine with an accumulation of cyclic AMP which is increased twofold after 6-hydroxydopamine treatment, while the cyclic AMP systems in slices from F-344 rat respond to norepinephrine with a relatively large accumulation of cyclic AMP which is not further increased after 6-hyxdroxydopamine treatment. The binding of WB 4101 to cerebral cortical membranes was similar in both rat strains and was unchanged after 6-hydroxydopamine treatment. The binding of dihydroalprenolol to membranes was similar in both rat strains and increased about 25% in both strains after 6-hydroxydopamine. Thus, the number of binding sites for these ligands does not correlate well with the magnitude of responses of cyclic AMP-generating systems to norepinephrine. Activity of cyclic AMP-phosphdiesterases in cerebral cortical homogenates was similar in both rat strains and was unchanged after 6-hydroxydopamine. Fluoride-stimulated adenylate cyclase activity in cerebral cortical homogenates appeared to be slightly higher in F-344 rats compared to Sprague-Dawley rats before but not after 6-hydroxydopamine treatment suggesting that changes in responsiveness of the cyclic AMP system might not be dependent upon changes in receptor density but in a post-receptor alteration such as adenylate cyclase activity.