Studies of platelet 5-hydroxytryptamine (serotonin) in storage pool disease and albinism.
Platelets in patients with storage pool disease are markedly deficient in a nonmetabolic (storage) pool of ADP that is important in platelet aggregation. They are also deficient in ATP, although to a lesser degree. In seven patients with this disorder, including one with albinism, platelet 5-hydroxytryptamine (5-HT) levels were reduced in proportion to the reduction in ATP (r = 0.94). Their platelets show diminished capacity to absorb [(14)C]5-HT, and the type of defect was similar to that produced in normal platelets by reserpine, a drug known to inhibit the uptake of 5-HT by the platelet dense granules. Storage pool-deficient platelets also converted more [(3)H]5-HT to [(3)H]5-hydroxyindoleacetic acid than did normal platelets, and the platelets in one of two patients studied contained increased amounts of 5-HT metabolites. The above findings, together with those reported previously, support the conclusion that the capacity of the dense granules (which may be either diminished or functionally abnormal) for storing 5-HT is decreased in storage pool disease; as a result, the 5-HT that enters the platelet may be more exposed to monoamine oxidases present on mitochondrial membranes. This diminished storage capacity (for 5-HT) may also explain why preincubating platelet-rich plasma with 5-HT for 45 min without stirring inhibits subsequent platelet aggregation by 5-HT to a greater degree in patients with storage pool disease than in normal subjects. The latter finding is also consistent with the theory that the aggregation of platelets by 5-HT is mediated by the same receptors on the plasma membrane that are involved in its uptake. The diminished release of platelet-bound [(14)C]5-HT by collagen that we found in these patients, as well as findings in previous studies, suggests that the release reaction may also be abnormal in storage pool disease.
D000244:Adenosine Diphosphate / Q000097:blood / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000097:blood; D000417:Albinism / Q000097:blood*; D001791:Blood Platelet Disorders / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000032:analysis / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002462:Cell Membrane; D002648:Child; D002854:Chromatography, Paper; D003094:Collagen / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D000431:Ethanol / Q000032:analysis; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000096:biosynthesis; D007211:Indoles / Q000032:analysis; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase; D010973:Platelet Adhesiveness / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium
D002250:Carbon Radioisotopes; D007211:Indoles; D014316:Tritium; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D000244:Adenosine Diphosphate; D012110:Reserpine; D000255:Adenosine Triphosphate; D003094:Collagen; D008995:Monoamine Oxidase; D004837:Epinephrine