On the pharmacology and biochemistry of the amine-uptake mechanism in human blood platelets

British Journal of Pharmacology
I C Campbell, A TODRICK


1. 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.


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