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On the pharmacology and biochemistry of the amine‐uptake mechanism in human blood platelets
Author(s) -
CAMPBELL I. C.,
TODRICK A.
Publication year - 1973
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1973.tb08373.x
Subject(s) - platelet , imipramine , ouabain , chemistry , pharmacology , mechanism of action , phenoxybenzamine , in vitro , serotonin , tricyclic , drug , biochemistry , medicine , stereochemistry , biology , receptor , sodium , alternative medicine , organic chemistry , pathology
Summary1 The uptake of 5‐hydroxytryptamine (5‐HT) by human blood platelets in vitro has been studied with the object of identifying the biochemical mechanisms involved. 2 Drugs active in adrenergic systems are only moderate inhibitors of uptake, although prenylamine is as active as the less potent tricyclic anti‐depressive drugs; phenoxybenzamine is almost inactive as a competitive inhibitor but is effective if pre‐incubated with the platelets beforehand. This parallels its pharmacological pattern of action. 3 Inhibitors of oxidative phosphorylation do not inhibit 5‐HT uptake, but iodoacetate inhibits, if pre‐incubated with the platelets; p ‐chloromercuribenzoate does also, when the platelets are suspended in synthetic medium, but not in plasma. 4 Ouabain causes significant inhibition at 10 −7 m ; by 10 −6 m it achieves its maximal effect, namely 40% inhibition; in K + ‐deficient medium, uptake falls to 30% of normal; the K + ‐dependent fraction of the uptake includes the ouabain‐sensitive component. Mg ++ has no effect. 5 A drug not possessing the imipramine structure, which has been tried in the treatment of depressive illness, 4‐phenyl bicyclo (2,2,2) octan‐1‐amine, is a highly potent inhibitor of 5‐HT uptake.