MOLECULAR PHARMAcoLoGY, 32:655-862 Relationship between a2-Adrenergic Receptor Binding Sites and the Functional Receptors Inhibiting Norepinephrine Release in Rat Cerebral Cortex1

The properties of cr2-adrenergic receptor binding sites and the receptors inhibiting [3H]norepinephnne (3H-NE) release from slices of cerebral cortex were compared. [3H]RX 781 094, an cr2-adrenergic receptor antagonist radioligand, labeled a single class of binding sites in membranes at 37#{176}with the pharmacological specificity expected of cr2-adrenergic receptors. 5’-Guanylimi-dodiphosphate (Gpp(NH)p) and NaCI caused small increases in the potencies of antagonists at the 3H-RX binding sites but decreased the potencies of agonists 4-22-fold. Antagonists blocked the inhibition of potassium-evoked 3H-NE release caused. by exogenous NE with potencies similar to those in competing for 3H-RX binding sites. Partial receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline(EEDQ) was used to determine whether there was a receptor reserve. EEDQ dose-dependently decreased both the density of 3H-RX binding sites and the maximal inhibition of 3H-NE release by different agonists