BINDING-PROPERTIES OF ALPHA-1 ADRENERGIC-RECEPTORS IN RAT CEREBRAL-CORTEX - SIMILARITY TO SMOOTH-MUSCLE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (3) , 605-612
Abstract
The characteristics of .alpha.1 adrenergic receptors in rat cerebral cortex were examined using the radioiodinated .alpha.1 adrenergic receptor antagonist [125I]BE 2254 [2-[.beta.-4-hydroxyphenyl)ethylamino methyl]tetralone] ([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 0.2-200 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. The Kd values for agonists and antagonists in inhibiting specific [125I]BE binding in rat cerebral cortex were highly correlated with their Kd values in inhibiting specific [125I]BE binding in rat vas deferens and with their equilibrium activation constants or pA2 [competitive antagonistic activity] values for activating or inhibiting .alpha.1 adrenergic receptor-mediated contraction of rat vas deferens. [125I]BE apparently labels .alpha.1 adrenergic receptors in rat cerebral cortex that are apparently identical to the .alpha.1 adrenergic receptors mediating contraction in rat vas deferens. Interactions of agonists and antagonists with these receptors are generally simple and competitive; however, small effects of physiological NaCl concentration were observed. The binding sites of these receptors can be inactivated with phenoxybenzamine.