SEROTONIN-STIMULATED PHOSPHOINOSITIDE TURNOVER - MEDIATION BY THE S-2 BINDING-SITE IN RAT CEREBRAL-CORTEX BUT NOT IN SUBCORTICAL REGIONS

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 234  (1) , 195-203
Abstract
In rat cerebral cortex, serotonin (5-HT) stimulates phosphoinositide turnover with an EC50 of 1 .mu.M in the presence of pargyline. The EC50 [median effective concentration] is 16-fold higher in the absence of pargyline. Selective S2 antagonists inhibit 5-HT-stimulated phosphoinositide turnover. Schild analysis of the blockade by ketanserin of the 5-HT effect gives an estimated Kd of ketanserin for the phosphoinositide-linked receptor of 11.7 nM, which agrees with the Kd (3.5 nM) of [3H]ketanserin for the S2 site. MK-212 [6-chloro-2-(1-piperazinyl)piperidine], 5-HT and 5-fluorotryptamine stimulate phosphoinositide turnover with potencies that resemble their potencies at the S2 but not the S1 binding site. Of 11 agonists tested, the tryptamine derivatives tend to be more efficacious then the piperazine derivatives. The selective S1 agonist 8-hydroxy-2-(di-N-propylamino)tetralin is inactive at stimulating phosphoinositide turnover. No significant relationship exists between the regional distributions of 5-HT-stimulated phosphoinositide turnover and S2 binding sites. The S2 antagonist ketanserin is less potent and less efficacious in hippocampus and limbic forebrain than in cerebral cortex. 5-HT-stimulated phosphoinositide turnover apparently is linked to the S2 binding site in rat cerebral cortex. However, 5-HT increases phosphoinositide turnover in subcortical regions by mechanisms other than stimulation of the S2 receptor.