Cyclic AMP opposes IP3-induced calcium release from permeabilized human platelets.

Abstract

Platelets permeabilized by means of a high voltage electric field demonstrated time- and ATP-dependent uptake of 45Ca++. Submicromolar concentrations of inositol-1,4,5-trisphosphate (IP3) caused a rapid release of 45Ca++ which was followed by a slower reuptake. Adenosine 3':5'-cyclic monophosphate (cAMP) did not affect 45Ca++ uptake but did reduce IP3-mediated calcium release in a concentration-dependent manner over the range of 1-100 microM. Because cAMP concentrations in this range occur following exposure of platelets to prostacyclin and other agents which interfere with platelet function, it is proposed that cAMP-mediated inhibition of the action of IP3 may play a role in the antithrombotic activity of compounds believed to elevate levels of this cyclic nucleotide.