The role of intracellular calcium in A-23187 stimulated and beta-adrenoceptor blocking drug treated blood platelets.
A significant concentration-dependent difference was found between beta-adrenoceptor blocking drugs in their ability to inhibit A23187-induced isolated platelet aggregation. In the absence of extracellular calcium ions the following rank order of potency to inhibit calcium ionophore stimulated platelet aggregation was shown: propranolol > bevantolol > alprenolol > metipranolol > oxprenolol > atenolol > pindolol > metoprolol approximately sotalol approximately practolol. The interruption of induced aggregation, as well as inhibition of aggregation, in the absence of extracellular calcium ions indicated interference of inhibitory beta-adrenoceptor blocking drugs with intramembrane or intraplatelet calcium pools activated with A23187. This suggestion was supported by the reversal of the inhibitory effect of beta-adrenoceptor blocking drugs in the presence of extracellular calcium ions. The effect was dose dependent and occurred within 30 sec after calcium administration. The results indicated that inhibitory beta-adrenoceptor blocking drugs, possessing a cationic amphiphilic structure, suppressed calcium mobilization in A23187-stimulated platelets, most probably after entering platelets. This explains why lipophilic drugs are more effective than hydrophilic ones in calcium ionophore A23187-stimulated platelets.
Nosál
R
R
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Jancinová
V
V
Petríková
M
M
D000319:Adrenergic beta-Antagonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D008297:Male; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D010975:Platelet Aggregation Inhibitors; D000001:Calcimycin; D002118:Calcium