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The nicotinic acetylcholine receptor of the bovine chromaffin cell, a new target for dihydropyridines.

Abstract：

:The effects of 1,4-dihydropyridine derivatives on divalent cation transients and catecholamine release stimulated by either high K+ or the nicotinic receptor agonist dimethyl-phenyl-piperazinium (DMPP) have been compared in bovine adrenal chromaffin cells. The activation of Ca2+ entry pathways was followed by measuring 45Ca2+ or Mn2+ uptake, or by the changes of [Ca2+]i in fura-2-loaded chromaffin cells. Various dihydropyridine Ca2+ channel blockers (nimodipine, PCA50938, nifedipine, nitrendipine, furnidipine) abolished the DMPP-mediated effects, but prevented only partially the activation by high [K+]0 of 45Ca2+ uptake. The IC50 for DMPP-induced activation was around 1 microM. The L-type Ca2+ channel activator Bay K 8644 potentiated the uptake of 45Ca2+ induced by K+ depolarization at concentrations between 10 nM and 1 microM, but completely inhibited the uptake of 45Ca2+ by DMPP (IC50, 0.9 microM). Both high [K+]0 and DMPP produced membrane depolarization as measured using bis-oxonol. The DMPP-evoked, but not the K(+)-evoked membrane depolarization was prevented by Na+ removal, suggesting that the depolarization was due to Na+ entry through the acetylcholine receptor ionophore. Nimodipine at 10 microM abolished the depolarization induced by DMPP, leaving the K(+)-evoked depolarization unaffected. Tetrodotoxin (2 microM) did not affect the DMPP- or high K(+)-mediated cell depolarization. Whole-cell inward current evoked by 100 microM DMPP (IDMPP) was measured in cells voltage-clamped at -80 mV. Nimodipine (10 microM) reduced IDMPP by 36%; Bay K 8644 (10 microM) inhibited IDMPP by 67%. DMPP-evoked catecholamine release from superfused chromaffin cells was reduced by over 90% with 10 microM nimodipine; in contrast, K(+)-evoked release was decreased by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

López MG,Fonteríz RI,Gandía L,de la Fuente M,Villarroya M,García-Sancho J,García AG

doi

10.1016/0922-4106(93)90078-n

subject

Has Abstract

pub_date

1993-10-15 00:00:00

pages

199-207

issue

2

eissn

0014-2999

issn

1879-0712

journal_volume

247

pub_type

杂志文章

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