Alteration of adenine nucleotide metabolism in coronary smooth muscle cells by activated platelets.
Cultured porcine coronary smooth muscle cells were preloaded with [3H]adenine and the inside and outside radioactive metabolites of the cells were analyzed following exposure to activated platelets. Incubation of the cells with human platelets activated by collagen enhanced intracellular conversion of ATP to ADP and caused dose- and time-dependent increase in radioisotopic release, mainly adenosine. Isolation of cyclic AMP revealed decreased cyclic AMP levels in the treated cells, both intra- and extracellularly. Of the substances released by the activated platelets, thromboxane A2 and serotonin enhanced radioisotopic release. The modulation of adenine metabolism by the activated platelets was preceded by increase in accumulation of inositol phosphates in the cells and was prevented by Iloprost (1 microM), a prostacyclin analog, cilostamide (10 microM), a cyclic AMP-specific phosphodiesterase inhibitor, or dibutyryl cyclic AMP (1 mM). Nifedipine showed only minor preventive effect. The agents which elevate cyclic AMP accumulation also attenuated phosphoinositide hydrolysis, whereas nifedipine had no effect. These results suggest that activated platelets may stimulate adenine metabolism in coronary smooth muscle cells, presumably due to activation of phosphoinositide turnover resulting in increased intracellular calcium. Enhanced adenosine release from the cells exposed to activated platelets may be a compensatory mechanism to prevent further platelet aggregation and contraction of coronary smooth muscle.
Kishi
Y
Y
Third Department of Medicine, Tokyo Medical and Dental University, Japan.
Ashikaga
T
T
Numano
F
F
D000225:Adenine / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000032:analysis; D016285:Iloprost / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D007295:Inositol Phosphates; D000242:Cyclic AMP; D000225:Adenine; D016285:Iloprost