INVOLVEMENT OF EPINEPHRINE IN THE PRESYNAPTIC BETA-ADRENOCEPTOR MECHANISM OF NOREPINEPHRINE RELEASE FROM RAT HYPOTHALAMIC SLICES

Abstract

Using high-performance liquid chromatography with an electrochemical detector, field impulse (5 or 2 Hz)- and high K+ (20 mM)-evoked release of endogenous norepinephrine from rat hypothalamic slices were measured. Release by impulses at 5 hZ was tetrodotoxin-sensitive and both types of release were Ca+2-dependent. Isoproterenol (10-10-10-8 M) dose-dependently facilitated impulse-evoked release and l-propranolol (10-8 M) shifted dose-effect curve of isopreterenol to the right. Atenolol (10-8-10-6 M) or butoxamine (10-9-10-8 M) .beta.-1 and .beta.-2-antagonist, respectively, dose-dependently antagonized the faciltatory effect of isoproterenol (10-8 M). Tazolol (10-8-10-7 M) .beta.-1-agonist, and salbutamol (10-10-10-8 M) .beta.-2-agonist, dose-dependently increased impulse-evoked release. Epinephrine (10-9 M) also facilitated impulse-evoked release and the action was antagonized by l-ropranolol (10-8 M). Isoproterenol (10-8 M) also faciltated high K+-evoked release in the presence of tetrodotoxin (3 .times. 10-7 M) to exclude possible involvement of axonal conduction or neuronal loops. This facilitatory effect was antagonized by l-propranolol (10-8 M). l-Propranolol (3 .times. 10-7 M) alone decreased release by impulses at 2 Hz, but the d-isomer produced no effect. When rats were pretreated with 2,3-dichloro-.alpha.-methylbenzylamine, an inhibitor of phenylethanolamine N-methyltransferase, the enzyme catalyzing the formation of epinephrine from norephinephrine, 80 mg/k i.p. before decapitation, the l-propranolol-induced decrease was abolished completely. Epinephrine contents in slices from rats pretreated wit 2,3-dichloro-.alpha.-methylbenzylamine were reduced to 38% of control, whereas norepinephrine contents were unchanged. There coexist presynaptic .beta.-1 and .beta.-2-receptors on noradrenergic nerve endings and epinephrine released from adrenergic nerve endings probably mediates the facilitatory mechanisms for norepinephrine release in the rat hypothalamus.