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Effects of β‐adrenoceptor antagonists on Ca 2+ ‐overload induced by lysophosphatidylcholine in rat isolated cardiomyocytes
Author(s) -
Chen Min,
Hashizume Hiroko,
Abiko Yasushi
Publication year - 1996
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.1476-5381.1996.tb15479.x
Subject(s) - pindolol , propranolol , atenolol , practolol , acebutolol , chemistry , endocrinology , medicine , ionomycin , timolol , lysophosphatidylcholine , pharmacology , calcium , biochemistry , phospholipid , intraocular pressure , membrane , phosphatidylcholine , blood pressure , ophthalmology
1 The effects of β‐adrenoceptor antagonists including (−)− and (+)‐propranolol, (−)− and (+)‐penbutolol, timolol, pindolol, atenolol, acebutolol and practolol on the Ca 2+ ‐overload induced by lysophosphatidylcholine (LPC) were examined in isolated cardiomyocytes of the rat. 2 Fura‐2 was used for measurement of the intracellular calcium concentration ([Ca 2+ ] i ). LPC (15 μ m ) produced a rapid increase in [Ca 2+ ] i from 72±5 to 3042±431 nM which coincided with a decrease in the percentage of rod‐shaped cells from 69±2 to 5±2%. 3 Preincubation with (−)−propranolol (20 μ m ), (+)‐propranolol (50 μ m ), or (−)− or (+)‐penbutolol (20 μ m ), the lipophilicity of which is higher than other β‐adrenoceptor antagonists, significantly inhibited both the increase in [Ca 2+ ] i and the cell‐shape change induced by 15 μ m LPC. The inhibitory effects of the four drugs on the LPC‐induced increase in [Ca 2+ ] i and cell‐shape change were concentration‐dependent. The IC 50 s of (−)−propranolol, (+)‐propranolol, (−)− and (+)‐penbutolol for the increase in [Ca 2+ ] i were 1.28, 10.50, 0.67 and 0.76 μ m , respectively. 4 Pretreatment with pindolol, timolol, acebutolol, practolol, atenolol or lignocaine did not inhibit the increase in [Ca 2+ ] i and the morphological change induced by LPC. 5 LPC markedly increased the release of creatine phosphokinase from 9±1 to 45±2% which could be significantly reduced by (−)− or (+)‐propranolol but not by acebutolol or timolol. 6 The protective effects of (−)− and (+)‐propranolol, (−)− and (+)‐penbutolol against the Ca 2+ ‐overload induced by LPC were not associated with the β‐adrenoceptor antagonistic action, but probably with an unknown action which is related to the preservation of membrane integrity. Further studies are necessary to clarify the exact mechanisms of the protective action of these β‐adrenoceptor antagonists against the Ca 2+ ‐overload induced by LPC.