Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aggregating effects of adenosine diphosphate, thrombin, 5-hydroxytryptamine, tryptamine, adrenaline and noradrenaline, and tri-ethyl tin have been carefully compared. The first three compounds in some circumstances produce remarkably similar effects although there are important differences. The kinetics of aggregation induced by adrenaline (and noradrenaline) are quite different and the tri-ethyl tin effects are different again. Anti-serotonins specifically inhibit 5-hydroxytryptamine and the anti-adrenaline drug phentolamine specifically inhibits the effects of the catecholamines. Experiments presented suggest but do not prove that aggregation produced by all these compounds is accompanied by the liberation of diphosphate from the platelets and that platelet triphosphate may be converted to diphosphate. How these different compounds all produce this effect is discussed. Either the presence of diphosphate or the action of a triphosphatase might be the immediate cause of aggregation if there is a single final common cause. The anti-adrenaline phentolamine prolongs the bleeding time, so adrenaline or noradrenaline may be involved in platelet phenomena in haemostasis.
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PMID:A COMPARISON OF PLATELET AGGREGATION PRODUCED BY SEVEN COMPOUNDS AND A COMPARISON OF THEIR INHIBITORS. 1415 60

The biogenesis of lysosome related organelles is defective in Hermansky-Pudlak syndrome (HPS), a disorder characterized by oculocutaneous albinism and platelet dense granule (DG) defects. The first animal model of HPS was the fawn-hooded rat, harboring a spontaneous mutation inactivating the small guanosine triphosphatase Rab38 This leads to coat color dilution associated with the absence of DGs and lung morphological defects. Another RAB38 mutant, the cht mouse, has normal DGs, which has raised controversy about the role of RAB38 in DG biogenesis. We show here that murine and human, but not rat, platelets also express the closely related RAB32. To elucidate the parts played by RAB32 and RAB38 in the biogenesis of DGs in vivo and their effects on platelet functions, we generated mice inactivated for Rab32, Rab38, and both genes. Single Rab38 inactivation mimicked cht mice, whereas single Rab32 inactivation had no effect in DGs, coat color, or lung morphology. By contrast, Rab32/38 double inactivation mimicked severe HPS, with strong coat and eye pigment dilution, some enlarged lung multilamellar bodies associated with a decrease in the number of DGs. These organelles were morphologically abnormal, decreased in number, and devoid of 5-hydroxytryptamine content. In line with the storage pool defect, platelet activation was affected, resulting in severely impaired thrombus growth and prolongation of the bleeding time. Overall, our study demonstrates the absence of impact of RAB38 or RAB32 single deficiency in platelet biogenesis and function resulting from full redundancy, and characterized a new mouse model mimicking HPS devoid of DG content.
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PMID:Combined deficiency of RAB32 and RAB38 in the mouse mimics Hermansky-Pudlak syndrome and critically impairs thrombosis. 3139 1