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In vitro adrenaline and collagen‐induced mobilization of platelet calcium and its inhibition by naftopidil, doxazosin and nifedipine
Author(s) -
Alarayyed N. A.,
Cooper M. B.,
Prichard B. N. C.,
Betteridge D. J.,
Smith C. C. T.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.00560.x
Subject(s) - chemistry , doxazosin , nifedipine , platelet , calcium , endocrinology , medicine , in vitro , pharmacology , biochemistry , organic chemistry , blood pressure
Aims The aim of the study was to obtain further information regarding the modes of action of doxazosin, naftopidil and nifedipine on platelet function. Methods We conducted an in vitro study of drug influences on adrenaline and collagen‐induced mobilization of platelet calcium. ‘fn2\ Results In the presence of fibrinogen (300 μg ml −1 ) both collagen (5 μg ml −1 ) and adrenaline (16 μm ) stimulated the aggregation of washed platelets. Collagen induced a transient rise (+4.97±0.63 μm ) in platelet Ca 2+ concentration, [Ca 2+ ] i , as measured using the photoprotein aequorin, which coincided with the onset of aggregation. Adrenaline induced a smaller rise (+3.6±0.96 μm ) which, however, occurred after the onset of aggregation. Naftopidil, an α 1 ‐adrenoreceptor antagonist produced a concentration‐dependent inhibition of collagen‐induced Ca 2+ mobilization, maximum inhibition (22.9±4%, P <0.05) occurring with 40 μm naftopidil. The inhibition of Ca 2+ mobilization was not reflected by a concentration‐dependent inhibition of platelet aggregation, although 40 μm naftopidil produced statistically significant inhibition (23.3±11.7%, P <0.05). The adrenaline‐induced rise in [Ca 2+ ] i was inhibited dose dependently by naftopidil (e.g. 40 μm naftopidil, 100±0%, P <0.05), as was aggregation (40 μm naftopidil, 100±0%, P <0.05). Doxazosin, another α 1 ‐adrenoreceptor blocker, inhibited Ca 2+ mobilization induced by collagen to similar extents as for naftopidil (30 μm doxazosin, 17.4±2.5%, P <0.05), but did not inhibit platelet aggregation. It also inhibited the adrenaline‐induced rise in [Ca 2+ ] i in a concentration‐dependent manner (30 μm doxazosin, 37.6±13.7%, P <0.05), significant inhibitions of platelet aggregation also being produced (30 μm, 49.6±17.2%, P <0.05). As expected, the calcium channel blocker nifedipine produced concentration‐dependent inhibitions of both collagen‐induced Ca 2+ mobilization (e.g. 28 μm nifedipine, 47.8±2.7%, P <0.05) and aggregation (28 μm, 55.1±9.2%, P <0.05). Conclusions These data indicate that the α 1 ‐adrenoreceptor blockers, naftopidil and doxazosin, inhibit Ca 2+ mobilization, this mechanism being possibly the means whereby these drugs inhibit platelet aggregation.