Premium
Sodium‐dependent inhibition by PN200‐110 enantiomers of nicotinic adrenal catecholamine release
Author(s) -
Cárdenas A.M.,
Montiel C.,
Artalejo A.R.,
SánchezGarcía P.,
García A.G.
Publication year - 1988
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.1476-5381.1988.tb16542.x
Subject(s) - chemistry , catecholamine , chromaffin cell , dihydropyridine , endocrinology , medicine , nicotinic agonist , calcium , pharmacology , adrenal medulla , receptor , biochemistry , biology , organic chemistry
1 Dimethylphenylpiperazinium (DMPP) or high K concentrations evoke catecholamine release from perfused cat adrenal glands; in both cases the secretory response was significantly enhanced in the absence of Na. Tetrodotoxin did not modify the nicotinic secretory response. 2 The (+)‐ and (−)‐enantiomers of the dihydropyridine Ca channel blocker PN200‐110 show a high degree of stereoselectivity in the inhibition of catecholamine secretion evoked by high K or by DMPP in the presence of Na, the (+)‐enantiomer being 57 and 80 times more potent, respectively, than the (−)‐enantiomer. Both, noradrenaline and adrenaline release were equally depressed by PN200‐110. 3 The IC 50 values for (+)‐ and (−)‐PN200‐110 for blockade of the secretory response induced by K or DMPP in the presence of Na are in the same range. In the absence of Na, (−)‐PN200‐110 did not affect DMPP‐evoked secretion; however, the (+)‐enantiomer partially inhibited it. 4 The results suggest that the physiological catecholamine release from chromaffin cells is preceded by Na entry through the nicotinic receptor‐associated ionophore; this causes cell depolarization, opening of voltage‐dependent, dihydropyridine‐sensitive Ca channels and Ca entry into the cell. In the absence of Na, additional Ca influx through an alternative pathway (the nicotinic cholinoceptor ionophore?) might also activate secretion.