Increase of human platelet serotonin uptake by atypical histamine receptors
Launay, J.M.; Bondoux, D.; Oset-Gasque, M.J.; Emami, S.; Mutel, V.; Haimart, M.; Gespach, C.
American Journal of Physiology 266(2 Pt 2): R526-R536
1994
ISSN/ISBN: 0002-9513 PMID: 8141412 Document Number: 424519
Histamine and the guanosine 3',5'-cyclic monophosphate (cGMP)-inducing agent sodium nitroprusside both increased serotonin (5-HT) uptake and cGMP levels in isolated human platelets in vitro. Histaminergic stimulation was observed at concentrations ranging from 10 nM to 0.25 mu-M (mean effective concentration (EC-50) = 0.1 mu-M histamine). The inhibition produced by the H-2-receptor antagonists tiotidine, metiamide, and cimetidine was 10-10-5 times more potent on histamine receptors regulating 5-HT uptake and cGMP generation in human platelets than on the histaminergic receptors H-1, H-IC, H-2, and H-3 in other tissues. The in vitro histamine-induced 5-HT uptake was prevented by preincubation of isolated human platelets in the presence of the nitric oxide synthase inhibitor N-G-monomethyl-L-arginine or the cGMP-lowering agent LY-83583. Histamine was ineffective in stimulating cAMP generation in human platelets and did not interact with effector sites known to down regulate 5-HT uptake, including imipramine, gamma-aminobutyric acid A, peripheral type benzodiazepine-binding sites, and V-1a vasopressin receptors inducing human platelet shape change and aggregation. These atypical human platelet histaminergic receptors differ from the previously classified histamine receptors by their apparent high affinity to histamine H-2-receptor antagonists and their apparent link with the soluble, nitric oxide-dependent guanylate cyclase. These findings suggest that human platelets express a new subtype H-2h of histamine receptors.