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Abstract

Activation of human blood platelets by arginine-vasopressin. Role of bivalent cations.

A Pletscher, P Erne, E Bürgisser and F Ferracin
Molecular Pharmacology December 1985, 28 (6) 508-514;
A Pletscher
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P Erne
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E Bürgisser
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F Ferracin
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Abstract

Arginine-vasopressin caused platelet activation, i.e., a shape change reaction and a rise in intracellular free Ca2+ ([Ca2+]i) only in the presence of certain bivalent cations. The EC50 of arginine-vasopressin (concentration causing half-maximal shape change) decreased with rising concentrations of Mn2+, Mg2+, or Ca2+ in the medium, but was at least an order higher with Ca2+ than with Mn2+ or Mg2+. The EC50 of the active bivalent cations (concentrations enabling 100 nM arginine-vasopressin to exert half-maximal shape change and rise in [Ca2+]i) varied with the individual cations, being by far the highest for Ca2+. The KD of [3H]arginine-vasopressin binding to platelet membranes and intact platelets markedly decreased when extracellular Mg2+ or Mn2+ were present, and the KD values were inversely related to the concentration of the cations. Ca2+ also lowered the KD values; however, the effect was less marked than that of Mg2+ or Mn2+ and, in physiological conditions, significant only in intact platelets. Vasopressin-1 antagonists counteracted arginine-vasopressin binding and the shape change reaction and [Ca2+]i rise induced by arginine-vasopressin. In the presence of Mn2+ in the medium, administration of arginine-vasopressin led to quenching of the intracellular fluorescence of 2-methyl-6-methoxy-8-nitroquinoline-loaded platelets, possibly due to influx of Mn2+. In conclusion, the dependency of the arginine-vasopressin-induced platelet activation on bivalent cations is at least partly due to an enhancement by these cations of the affinity of the vasopressin-1 receptor for arginine-vasopressin. Thereby, under physiological conditions, Mg2+ seems to be of primary importance. Other mechanisms may be involved, too, e.g., an enhancement by arginine-vasopressin of the influx of bivalent cations into the platelets.

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Molecular Pharmacology
Vol. 28, Issue 6
1 Dec 1985
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Abstract

Activation of human blood platelets by arginine-vasopressin. Role of bivalent cations.

A Pletscher, P Erne, E Bürgisser and F Ferracin
Molecular Pharmacology December 1, 1985, 28 (6) 508-514;

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Abstract

Activation of human blood platelets by arginine-vasopressin. Role of bivalent cations.

A Pletscher, P Erne, E Bürgisser and F Ferracin
Molecular Pharmacology December 1, 1985, 28 (6) 508-514;
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