AUTO-REGULATION OF ENDOGENOUS EPINEPHRINE RELEASE VIA PRESYNAPTIC ADRENOCEPTORS IN THE RAT HYPOTHALAMIC SLICE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 235  (1) , 248-253
Abstract
High-K+(30 mM)-evoked release of endogenous epinephrine in hypothalamic slices from three rats in the presence of tetrodotoxin, 3 .times. 10-7 M, was measured by high-performance liquid chromatography with an electrochemical detector. Spontaneous and evoked release of epinephrine was markedly reduced, when rats were pretreated with 2,3-dichloro-.alpha.-methylbenzylamine, an inhibitor of phenylethanolamine N-methyltransferase, the enzyme catalyzing the formation of epinephrine from norepinephrine, 80 mg/kg i.p., before decapitation. The amount of epinephrine released during the resting state was lower by a factor of approximately 2 orders than that of norepinephrine and dopamine but was consistently higher than the limit of the sensitivity of this assay system, 0.1 to 0.3 pmol. The evoked release of epinephrine was Ca++ dependent. Isoproterenol, 10-8 M to 10-7 M, dose dependently increased this parameter. l-Propranolol, 3 .times. 10-8 M, shifted the dose-effect curve of isoproterenol to the right. Atenolol, 10-6 M, and butoxamine, 3 .times. 10-8 M, beta-1 and beta-2 antagonists, respectively, antagonized the action of isoproterenol, 3 .times. 10-8 M. Tazolol, 3 .times. 10-7 and 10-6 M, a beta-1 agonist, and salbutamol, 10-8 and 3 .times. 10-8 M, a beta-2 agonist, dose dependently increased the evoked release of epinephrine. l-Propranolol, 3 .times. 10-7 M and 3 .times. 10-6 M alone, dose dependently decreased this parameter, but the d-isomer produced no effect. Clonidine, 10-8 and 10-7 M, an alpha-2 agonist, dose dependently decreased the parameter, and this decrease was antagonized by yohimbine, 10-6 M, an alpha-2 antagonist. Methoxamine, 10-8 and 10-7 M, an alpha-1 agonist, produced no effect. Yohimbine, 10-6 M alone, increased the parameter, whereas prazosin, an alpha-1 antagonist, produced no effect. l-Sulpiride, 10-8 and 10-7 M, a dopaminergic antagonist, also produced no effect. We conclude that, in the rat hypothalamus, there are coexisting presynaptic inhibitory alpha-2 and facilitatory beta-1 and beta-2 receptors on adrenergic nerve terminals and that the epinephrine released may mediate physiological autoregulatory feedback mechanisms for further release of epinephrine.