Involvement of epinephrine in the presynaptic beta adrenoceptor mechanism of norepinephrine release from rat hypothalamic slices.
Using high-performance liquid chromatography with electro-chemical detector, we measured field impulse (5 or 2 Hz)- and high K+ (20 mM)-evoked release of endogenous norepinephrine from rat hypothalamic slices. Release by impulses at 5 Hz was tetrodotoxin-sensitive and both types of release were Ca++-dependent. Isoproterenol (10(-10) to 10(-8) M) dose-dependently facilitated impulse-evoked release and l-propranolol (10(-8) M) shifted dose-effect curve of isoproterenol to the right. Atenolol (10(-8) to 10(-6) M) or butoxamine (10(-9) to 10(-8) M), beta-1 and beta-2-antagonist, respectively, dose-dependently antagonized the facilitatory effect of isoproterenol (10(-8) M). Tazolol (10(-8) to 10(-7) M), beta-1-agonist, and salbutamol (10(-10) to 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-propranolol (10(-8) M). Isoproterenol (10(-8) M) also facilitated high K+-evoked release in the presence of tetrodotoxin (3 X 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 X 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 norepinephrine, 80 mg/kg i.p. before decapitation, the l-propranolol-induced decrease was abolished completely.(ABSTRACT TRUNCATED AT 250 WORDS)
Ueda
H
H
Goshima
Y
Y
Kubo
T
T
Misu
Y
Y
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D004558:Electric Stimulation; D004837:Epinephrine / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D001596:Benzylamines; D011943:Receptors, Adrenergic, beta; C002569:2,3-dichloro-alpha-methylbenzylamine; D011433:Propranolol; D007545:Isoproterenol; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine