SHAPE CHANGE OF BLOOD PLATELETS—A MODEL FOR CEREBRAL 5‐HYDROXYTRYPTAMINE RECEPTORS?

In rabbit blood platelets, tryptamine, serotonin (5-HT), and related compounds like quipazine and mescaline caused a shape change, which was blocked by low concentrations of methysergide. The most potent blockers of the serotonin-induced shape change were ergoline derivatives and neuroleptic drugs, showing high stereoselectivity. LSD, psilocine, and some dimethylated tryptamines acted as mixed agonist-antagonists. Compounds that were agonists or mixed agonist-antagonists on platelets also act as serotonin agonists in the central nervous system. However, platelet serotonin receptors responded differently to antagonists than those in brain areas with dense serotonin innervation, but similarly to receptors in spinal cord, cerebral cortex, and reticular formation. Platelets may serve as cautious models for some, but not all, central serotonin receptors.

Study at a glance

Abstract

In blood platelets of rabbits isolated by a stractan gradient and incubated in a protein‐poor medium, tryptamine, 5‐hydroxytryptamine (5‐HT) and derivatives, quipazine and mescaline caused a shape change. This shape change was inhibited by low concentrations of methysergide. The most potent antagonists of the 5‐HT‐induced shape change included ergoline derivatives and neuroleptic drugs, which showed high stereoselectivity. (‐f)‐Lysergic acid diethylamide ((+)‐LSD), psilocine and some N',N′‐dimethylated tryptamines acted as mixed agonist‐antagonists. The compounds found to be agonists or mixed agonist‐antagonists on platelets have previously been shown to act also as 5‐HT agonists in the central nervous system (CNS). With regard to 5‐HT antagonists, the 5‐HT receptors of platelets reacted differently from those described earlier in brain areas with dense 5‐hydroxytryptaminergic innervation, but showed similarities to 5‐HT receptors investigated previously in spinal cord, cerebral cortex and possibly reticular formation. It is concluded that platelets may be considered with caution as models for some, but not for all, 5‐HT receptors in the CNS.