PT  - JOURNAL ARTICLE
AU  - A Pletscher
AU  - P Erne
AU  - E Bürgisser
AU  - F Ferracin
TI  - Activation of human blood platelets by arginine-vasopressin. Role of bivalent cations.
DP  - 1985 Dec 01
TA  - Molecular Pharmacology
PG  - 508--514
VI  - 28
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/28/6/508.short
4100  - http://molpharm.aspetjournals.org/content/28/6/508.full
SO  - Mol Pharmacol1985 Dec 01; 28
AB  - 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.