Role of Ca2+ and protein kinase C in the serotonin (5-HT) transport in human platelets

被引:21
作者
Turetta, L
Bazzan, E
Bertagno, K
Musacchio, E
Deana, R
机构
[1] Univ Padua, Dipartimento Chim Biol, CNR, Unit Study Biomembranes, I-35121 Padua, Italy
[2] Univ Padua, Dept Med & Surg Sci, Padua, Italy
关键词
D O I
10.1016/S0143-4160(02)00052-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Accumulation of serotonin l into human platelets was not affected by the presence of the extra-cellular calcium chelator EGTA, while decreased by platelet incubation with the membrane permeant chelator BAPTA-AM. Serotonin uptake also diminished upon platelet exposure to EGTA/thapsigargin or EGTA/ionomycin which increased the cytosolic [Ca(2+)] to levels lower than those inducing secretion of dense granules. The latter inhibition depended in part on changes of intra-granular pH, since the accumulation of acridine orange, which is driven into the dense granules by the intra-granular acid pH gradient, was slightly decreased in the presence of EGTA/thapsigargin. These compounds also inhibited the 5-HT uptake in platelets pre-incubated with reserpine and bafilomycin that prevent 5-HT from entering into the dense granules. Inhibitors of protease, protein phosphatase, Na(+)/H(+) exchanger or ciclo-oxygenase activities did not modify the serotonin accumulation. Addition of EGTA/thapsigargin to reserpine-treated, [(14)C]5-HT-loaded, platelets caused an imipramine-insensitive release of labelled serotonin. This release was reduced by both BAPTA-AM or protein kinase C inhibitor bisindoylmaleimide (GF). The latter compound, either alone or together with EGTA/thapsigargin, inhibited the 5-HT accumulation in reserpine-treated platelets. It is concluded that both cytosolic [Ca(2+)] and protein kinase C are involved in the regulation of the plasma membrane 5-HT transport. (C) 2002 Published by Elsevier Science Ltd.
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页码:235 / 244
页数:10
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