title: Effects of dihydropyridines and inorganic calcium blockers on aggregation and on intracellular free calcium in platelets.
abstract: [Ca2+]i increase is necessary in physiological platelet activity, particularly aggregation and release. The increase of [Ca2+]i observed during platelet activation depends in part on Ca2+ influx from the extracellular medium. The participation of voltage-operated Ca2+ channels as a pathway for Ca2+ entry is controversial. In the present study we have attempted to reinvestigate this problem by measuring aggregation and [Ca2+]i changes in platelets activated by ADP or thrombin and incubated with organic or inorganic blockers of calcium channels. The main findings of the present paper can be summarized as follows: (i) Ni2+, Co2+ and Mn2+, well known inorganic blockers of Ca2+ channels, inhibited platelet aggregation induced by ADP or thrombin in a dose-dependent manner, Ni2+ being the most effective agent. (ii) Thrombin induced a rise in free [Ca2+]i in platelets incubated both in 1 mmol/l Ca(2+)-containing medium and in nominally Ca(2+)-free medium; the rise of free [Ca2+]i was in the first case up to 370 +/- 31 nmol/l and in the second case up to 242 +/- 26 nmol/l, indicating that this observed difference was due to Ca2+ entry from the extracellular medium. Co2+ and Ni2+ abolished that difference by inhibiting Ca2+ influx. (iii) Nisoldipine, nitrendipine and nimodipine (10-50 nmol/l) inhibited in a dose-dependent manner platelet aggregation induced by either ADP or thrombin in platelets incubated in normal-Ca2+ normal-K+ medium, also, aggregation was inhibited to a similar extent in platelets incubated in normal-Ca2+ high-K+ medium. (iv) Nisoldipine--the most effective dihydropyridine to inhibit platelet aggregation--also inhibited Ca2+ influx in platelets incubated in normal-Ca2+ medium, either in normal-K+ or high-K+ media. Our data support the existence of voltage-operated, dihydropyridine-sensitive calcium channels (L-type) and a physiological role for them in platelet function.
authors.affiliation: Laboratori de Neurofisiologia i Biomembranes, Unitat de Fisiologia Humana--Facultat de Medicina, Universitat de Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Palés
authors.forename: L
authors.initials: L
authors.lastname: Palacios-Araus
authors.forename: A
authors.initials: A
authors.lastname: López
authors.forename: A
authors.initials: A
authors.lastname: Gual
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage; D015737:Nisoldipine / Q000008:administration & dosage; D009568:Nitrendipine / Q000008:administration & dosage; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010975:Platelet Aggregation Inhibitors; D015737:Nisoldipine; D009553:Nimodipine; D000244:Adenosine Diphosphate; D009568:Nitrendipine; D013917:Thrombin; D011188:Potassium; D002118:Calcium