Inhibition of adrenomedullary catecholamine release by propranolol isomers and clonidine involving mechanisms unrelated to adrenoceptors.
1 Transmural electrical stimulation (10 Hz, 40 V, 1 ms for 60s) increased total catecholamine secretion from perfused cat adrenal glands; this response 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 (IC50 = 24 nM). 3 Either, racemic propranolol or the (+)- or (-)-isomers (1-10 microM) equally inhibited [3H]-noradrenaline release evoked by nicotine or acetylcholine from cultured bovine adrenal chromaffin cells; clonidine (10 microM) 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 alpha- or beta-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.
Orts
A
A
Departamento de Neuroquímica, Universidad de Alicante, Facultad de Medicina, Spain.
Orellana
C
C
Cantó
T
T
Ceña
V
V
González-García
C
C
García
A G
AG
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002415:Cats; D002417:Cattle; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013237:Stereoisomerism
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009553:Nimodipine; D011433:Propranolol; D003000:Clonidine; D011188:Potassium