PMID- 1333596 OWN - NLM STAT- MEDLINE DCOM- 19921231 LR - 20190902 IS - 0901-9928 (Print) IS - 0901-9928 (Linking) VI - 71 IP - 4 DP - 1992 Oct TI - Exogenous GTP increases cyclic GMP and inhibits thrombin-induced aggregation of washed human platelets: comparison with ATP, adenosine and guanosine. PG - 289-93 AB - The effects of exogenous guanosine 5'-triphosphate (GTP), guanosine, adenosine 5'-triphosphate (ATP) and adenosine on platelet aggregation, serotonin secretion and cyclic nucleotide accumulation were studied using thrombin-stimulated washed human platelets. GTP (10 microM-1 mM) dose-dependently inhibited thrombin-induced aggregation and serotonin secretion. The inhibition of aggregation was accompanied by an increase in platelet cyclic GMP. GTP did not affect cyclic AMP concentration. Adenosine (1 microM-1 mM) dose-dependently inhibited thrombin-induced aggregation and serotonin secretion, and increased cyclic AMP. ATP at high concentrations (100 microM-1 mM) inhibited aggregation and serotonin secretion, and 1 mM ATP increased cyclic AMP. Guanosine was relatively ineffective in preventing aggregation and serotonin secretion and did not affect cyclic GMP. The rank order of inhibition of thrombin-induced aggregation of washed human platelets was adenosine > GTP > ATP > guanosine. In conclusion, exogenous GTP inhibits thrombin-induced aggregation and serotonin secretion of washed human platelets by increasing cyclic GMP. The results raise the possibility of a cell membrane site of action for GTP in platelets which mediates the activation of soluble guanylate cyclase suggesting that GTP may have a local antithrombotic effect also in vivo. FAU - Vuorinen, P AU - Vuorinen P AD - Department of Biomedical Sciences, University of Tampere, Finland. FAU - Laustiola, K E AU - Laustiola KE LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Denmark TA - Pharmacol Toxicol JT - Pharmacology & toxicology JID - 8702180 RN - 0 (Platelet Aggregation Inhibitors) RN - 12133JR80S (Guanosine) RN - 333DO1RDJY (Serotonin) RN - 86-01-1 (Guanosine Triphosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 3.4.21.5 (Thrombin) RN - H2D2X058MU (Cyclic GMP) RN - K72T3FS567 (Adenosine) SB - IM MH - Adenosine/pharmacology MH - Adenosine Triphosphate/*pharmacology MH - Blood Platelets/*drug effects MH - Cyclic GMP/*metabolism MH - Guanosine/pharmacology MH - Guanosine Triphosphate/*pharmacology MH - Humans MH - Platelet Aggregation/*drug effects MH - Platelet Aggregation Inhibitors/*pharmacology MH - Serotonin/metabolism MH - Thrombin/*antagonists & inhibitors/pharmacology EDAT- 1992/10/01 00:00 MHDA- 1992/10/01 00:01 CRDT- 1992/10/01 00:00 PHST- 1992/10/01 00:00 [pubmed] PHST- 1992/10/01 00:01 [medline] PHST- 1992/10/01 00:00 [entrez] AID - 10.1111/j.1600-0773.1992.tb00985.x [doi] PST - ppublish SO - Pharmacol Toxicol. 1992 Oct;71(4):289-93. doi: 10.1111/j.1600-0773.1992.tb00985.x.