Mediation of Norepinephrine-Stimulated Cyclic AMP Accumulation by Adrenergic Receptors in Hypothalamic and Preoptic Area Slices: Effects of Estradiol

Abstract

Adrenergic receptor agonists and antagonists were employed to establish (a) which receptor subtypes mediate the cyclic AMP response to norepinephrine in hypothalamic and preoptic area slices from gonadectomized female rats and (b) which receptor subtypes might be modulated by the steroid hormone estradiol. Slice cyclic AMP levels were elevated by the .beta. receptor agonist isoproterenol, but not by .alpha.1 (phenylephrine, methoxamine) or .alpha.2 (clonidine) agonists. However, the .alpha. agonist phenylephrine potentiated the effect of the .beta. agonist isoproterenol on slice cyclic AMP accumulation. In slices from rats given no hormone treatment, the .beta. antagonist propranolol inhibited norepinephrine-stimulated cyclic AMP production, while the .alpha.1 antagonist prazosin was without effect. In contrast, the cyclic AMP response to norepinephrine in slices from estradiol-treated rats was blocked more effectively by prazosin than by propranolol. Estradiol treatment also attentuated the production of cyclic AMP by the .beta. agonist isoproterenol. The data suggest (a) that norepinephrine induction of cyclic AMP accumulation in hypothalamic and preoptic area slices is mediated by .beta. receptor and potentiated by .alpha. receptor activation and (b) that estradiol depressers .beta. and increase .alpha.1 receptor function in slices from brain regions associated with reproductive physiology.