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Inhibition of adrenomedullary catecholamine release by propranolol isomers and clonidine involving mechanisms unrelated to adrenoceptors
Author(s) -
Orts Alfredo,
Orellana Carmen,
Cantó Tomás,
Ceña Valentín,
GonzálezGarcía Carmen,
García Antonio G.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11383.x
Subject(s) - yohimbine , propranolol , endocrinology , medicine , acetylcholine , catecholamine , chemistry , isoprenaline , adrenal medulla , splanchnic nerves , clonidine , cholinergic , stimulation , biology , receptor , antagonist
1 Transmural electrical stimulation (10 Hz, 40 V, 1 ms for 60 s) increased total catecholamine secretion from perfused cat adrenal glands; this respnse was enhanced by neostigmine and inhibited by mecamylamine, suggesting that release of acetylcholine from splanchnic nerve terminals was stimulating nicotinic receptors and enhancing catecholamine secretion. 2 Isoprenaline, (‐)‐propranolol and (+)‐propranolol (10 −7 ‐10 −5 m ) inhibited the electrically‐evoked secretory response by 40–70%; similar reductions were obtained with clonidine and yohimbine. Neither, (+)‐propranolol nor (‐)‐propranolol inhibited K‐evoked secretion from cat adrenals; in contrast, nimodipine potently inhibited it (IC 50 = 24 n m ). 3 Either, racemic propranolol or the (+)‐ or (‐)‐isomers (1–10 μ m ) equally inhibited [ 3 H]‐noradrenaline release evoked by nicotine or acetylcholine from cultured bovine adrenal chromaffin cells; clonidine (10 μ m ) inhibited secretion by 50% and yohimbine or isoprenaline did not affect it. 4 The results indicate that adrenomedullary catecholamine release evoked by splanchnic nerve stimulation is not modulated by α‐or β‐adrenoceptors and suggest that propranolol may inhibit secretion by blocking ion fluxes through the acetylcholine receptor ionophore. Clonidine may inhibit secretion by this same mechanism, and/or by interfering with some intracellular event in the secretory mechanism.