Conditions that lithium inhibits or potentiates vasopressin V1-receptor-mediated platelet aggregation and [Ca++]i mobilization.
1. Besides clinical use, there are many explanations for the mechanism of action of lithium. Although it is shown that lithium may reduce the supply of inositol that is required to sustain phosphoinositide synthesis, evidence exists concerning the potentiating effect of lithium on this pathway. We therefore decided to evaluate conditions in which lithium inhibits or potentiates platelet aggregation and calcium response induced by vasopressin. 2. Platelet aggregation was measured by the photometric method, and changes in intracellular free calcium were measured using fura-2/AM. 3. We show an inhibitory action of neomycin on vasopressin-induced platelet aggregation. Lithium, according to the preincubation time, could both potentiate or inhibit platelet aggregation and calcium responses induced by vasopressin. The inhibitory effect of lithium on platelet aggregation is dependent on concentrations of both lithium and vasopressin and also the presence of indomethacin, for example, in the absence of indomethacin there was no clear inhibitory action of lithium on vasopressin-induced platelet aggregation. 4. These results show the importance of arachidonate metabolites concerning lithium effects on platelet V1-receptor signaling. In conclusion, because the arachidonate metabolites are responsible for the release of other active substances from platelets' granules, the aggregatory responses in the absence of indomethacin may be amplified, and this subsequently may change the net inhibitory action of lithium.
Dehpour
A R
AR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Kiani
K
K
Ghafourifar
P
P
Mousavizadeh
K
K
D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017483:Receptors, Vasopressin / Q000187:drug effects* / Q000502:physiology
D010716:Phosphatidylinositols; D010975:Platelet Aggregation Inhibitors; D017483:Receptors, Vasopressin; D016718:Arachidonic Acid; D008094:Lithium; D009355:Neomycin; D002118:Calcium