Antithrombotic nipecotamide increases cyclic AMP levels and inhibits protein phosphorylation in human platelets

Abstract α,α′-bis[3-( N ′, N -diethylcarbamoyl)piperidino]- p -xylene dihydrobromide (A-1), a typical antithrombotic nipecotamide, elevated the levels of cyclic adenosine monophosphate (cAMP) in human platelets in vitro , without inhibiting cAMP-phosphodiesterase (PDE). The compound elevated the basal cAMP levels, enhanced the prostaglandin (PG)E 1 -stimulated platelet adenylyl cyclase (AC) activity, and prevented the ADP-induced decline of the latter. Collagen-induced phosphorylation of 20 and 47 kDa proteins was inhibited by IC 50 and 0.5 × IC 50 concentrations. In light of the known actions of A-1, it is suggested that stimulation of AC and inhibition of agonist-induced rise in cytosolic ionized calcium ([Ca 2+ ] 1 ) may constitute an aspect of its mechanism of action.