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Mechanism of Neurotransmitter Release Elicited by the Preferential α 1 ‐Adrenergic Receptor Agonist Phenylephrine in Superfused Superior Cervical Ganglion Cells in Culture
Author(s) -
Schwartz Dean D.,
Malik K. U.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08226.x
Subject(s) - phenylephrine , methoxamine , agonist , chemistry , efflux , endocrinology , medicine , pharmacology , receptor , biology , biochemistry , blood pressure
Phenylephrine increased [ 3 H]norepinephrine efflux and accumulation of cyclic AMP in cultured rat superior cervical ganglion cells supervised with Tyrode's solution. The purpose of this study was to determine the mechanism and relationship between these two events. Electrical stimulation (1–2 Hz), potassium chloride (50 m M ), and the preferential α 1 ‐adreneargic receptor agonist phenylephrine (1–100 μ M ) increased fractional tritium efflux, whereas methoxamine, cirazoline, and amidephrine were relatively ineffective. Phenylephrine, but not methoxamine and cirazoline, also iacreased cyclk AMP accumulation. Phenylephrine‐induced tritium efflux was not altered by α‐and β‐adrenergic receptor antagonists or by removal of extracellular calcium. Phenylephrine‐induced cyclic AMP accumulation was blocked by the β‐adrenergic receptor antagonists propranolol and atenokd. Focskolin (10 μ M ) and the nonhydrolyzable cyclic AMP analogue 8‐(4‐chlorophenylthio)cyclic AMP (100 μ M ) had minimal effect on tritium efflux. However, phenylephrine‐evoked increase in tritium efflux was dose dependency attenuated by the neuronal uptake blocker cocaine, and phenylephrine dose‐dependently inhibited the incorporation of [ 3 H]norepinephrine into neuronal stores. We conclude that the increase in tritium efflux induced by Phenylephrine is independent of cyclic AMP accumulation and appears to be mediated by uptake of phenylephrine via the neuronal carrier‐mediated amine transport process, which in tarn promotes efflux of the adrenergic transmitter from its storage sites.