Abstract
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)
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|