Effect of ?-methylserotonin on serotonin receptor-coupled phosphoinositide breakdown in rat cerebral cortex.
?-Methylserotonin, an analogue of serotonin formed in vivo from ?-methyltryptophan, is able to stimulate phosphoinositide turnover (up to 190% of the basal rate) in slices of rat cerebral cortex in vitro. Desensitization of the cortical slices by ?-methylserotonin or serotonin significantly decreases serotonin-stimulated (but not norepinephrine-stimulated) phosphoinositide turnover, thus indicating an interaction of ?-methylserotonin with serotonin receptors. Ketanserin, a serotonin(2)-receptor antagonist, blocks ?-methylserotonin-stimulated phosphoinositide turnover. This suggests that this action is mediated by serotonin(2)-receptors. The chronic administration to rats of p-chlorophenylalanine, which depletes stores of brain serotonin, increases serotonin-stimulated phosphoinositide turnover, as detected in vitro. In contrast to this, the chronic administration of ?-methyltryptophan, which also depletes brain serotonin, does not increase the in vitro serotonin-stimulated phosphoinositide turnover. This suggests that accumulated ?-methylserotonin formed in the brain substitutes for serotonin and prevents the up-regulation of serotonin-receptor-mediated phosphoinositide hydrolysis. The present study explains the molecular basis for the functional activity of ?-methylserotonin in serotonergic neurons.
Regunathan
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Departments of Biochemistry and Psychiatry, McGill University, Montreal, Quebec Canada; Douglas Hospital Research Centre, Verdun, Quebec, Canada.
Sourkes
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TL