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Separation of two pathways for calcium entry into chromaffin cells
Author(s) -
Gandía Luis,
Casado LuisFelipe,
López Manuela G.,
García Antonio G.
Publication year - 1991
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.1476-5381.1991.tb12302.x
Subject(s) - calcium , chromaffin cell , chemistry , neuroscience , biology , microbiology and biotechnology , adrenal medulla , catecholamine , organic chemistry
1 The effects of various drugs on 45 Ca + 40 Ca uptake into cultured bovine adrenal chromaffin cells evoked by 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP) or high K, were studied. In the presence of 1 m m external 40 Ca, with 45 Ca as a radiotracer, unstimulated cells took up an average of 0.13 fmol/cell 40 Ca and 772 c.p.m./10 6 cells of 45 Ca ( n = 76). Upon stimulation with DMPP (100μ m for 60s) or K (59 m m for 60s), Ca uptake increased to 0.92 and 1 fmol/cell, respectively. 2 Flunarizine behaved as a potent blocker of both DMPP‐ and K‐evoked Ca uptake (IC 50 of 1.76 and 1.49 μ m , respectively for DMPP and K). A similar picture emerged with Cd ions, though Cd exhibited an IC 50 against K (1.86 μ m ) slightly lower than the IC 50 against DMPP (8.14 μ m ). 3 Clear cut differences were observed with amiloride, guanethidine, nimodipine and nisoldipine which behaved as selective blockers of DMPP‐mediated Ca uptake responses: IC 50 values to block DMPP effects were 290, 27, 1.1 and 1.63 μ m respectively for amiloride, guanethidine, nimodipine and nisoldipine. Amiloride blocked K‐evoked Ca uptake by only 35% and guanethidine did not affect it. Nisoldipine inhibited K‐evoked Ca uptake only partially at low concentrations (about 30%); a second blocking component was observed at the highest concentration used (10 μ m ). At 10 μ m , nimodipine blocked K‐evoked Ca uptake by 50%. 4 Thus, it seems that the nicotinic receptor mediated Ca uptake pathway can be pharmacologically separated from the K‐activated pathway. The results are compatible with the hypothesis that in cultured bovine adrenal chromaffin cells, stimulation of nicotinic receptors recruits a single type of Ca channel which is sensitive to flunarizine, Cd, amiloride, guanethidine, nimodipine and nisoldipine. The results also suggest that K depolarization might be recruiting in addition to this channel, another Ca channel which is highly sensitive to Cd and flunarizine, resistant to nisoldipine, nimodipine and amiloride, and insensitive to guanethidine.