Binding properties of alpha-1 adrenergic receptors in rat cerebral cortex: similarity to smooth muscle.

The characteristics of alpha-1 adrenergic receptors in rat cerebral cortex were examined using the radioiodinated alpha-1 adrenergic receptor antagonist [125I]BE 2254 [( 125I]BE). [125I]BE labeled a single class of high-affinity binding sites in a particulate fraction of rat cerebral cortex with mass action kinetics and a KD of 57 pM. The binding of [125I]BE was inhibited by various alpha adrenergic receptor antagonists, partial agonists and full agonists. The potency of these compounds in competing for the [125I]BE binding sites suggested that [125I]BE was labeling alpha-1 adrenergic receptors in rat cerebral cortex. In the absence of a physiological concentration of NaCl in the assay medium there was a small (20%) decrease in the density of [125I]BE binding sites with no effect on the KD value. The absence of NaCl also caused a 4-fold increase in the potency of norepinephrine in competing for [125I]BE binding sites. All drugs competed for [125I] BE binding sites with Hill coefficients greater than 0.86, except for oxymetazoline which had a Hill coefficient of 0.77. Scatchard analysis of specific [125I]BE binding in the presence of various competing drugs showed that the inhibition by both agonists and antagonists was purely competitive, but the inhibition by oxymetazoline was complex. Treatment of the particulate fraction of rat cerebral cortex with 0.2 to 200 nM phenoxybenzamine for 10 min caused a dose-dependent decrease in the density of [125I] BE binding sites which could be mostly blocked by the presence of norepinephrine during the phenoxybenzamine exposure.(ABSTRACT TRUNCATED AT 250 WORDS)