Antithrombotic nipecotamide increases cyclic AMP levels and inhibits protein phosphorylation in human platelets.
alpha,alpha'-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)E1-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 IC50 and 0.5 x IC50 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 ([Ca2+]i) may constitute an aspect of its mechanism of action.
Handa
R K
RK
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Dillingham
E O
EO
Gollamudi
R
R
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology*; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D001798:Blood Proteins; D009557:Nipecotic Acids; D010975:Platelet Aggregation Inhibitors; C043099:alpha, alpha'-bis(3-(N,N-diethylcarbamoyl)piperidino)-4-xylene; D000244:Adenosine Diphosphate; D003094:Collagen; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000527:Alprostadil