5-Hydroxytryptamine-stimulated inositol phospholipid hydrolysis in rat cerebral cortex slices: pharmacological characterization and effects of antidepressants.
The ability of 5-hydroxytryptamine (5-HT) and related agonists to stimulate hydrolysis of inositol phospholipids was examined in rat cerebral cortex slices using a direct assay which involves prelabeling with [3H]inositol and assaying [3H]inositol phosphates in the presence of lithium. 5-HT agonists stimulated [3H]inositol phosphate accumulation in a dose-related but biphasic manner and only the high-affinity component of the dose-response curve was sensitive to antagonists. This response to 5-HT was blocked potently by ketanserin and other putative 5-HT2 antagonists but the overall pattern of apparent drug affinities was inconsistent with that seen at 5-HT2 sites labeled with [3H]ketanserin in cortical membranes. Pretreatment of slices with the alkylating antagonist phenoxybenzamine reduced the inositol phospholipid response to 5-HT to a greater extent than the suppression of [3H]ketanserin binding. Similarly, chronic but not acute treatment of rats with the antidepressants iprindole and imipramine resulted in a greater loss of 5-HT-induced inositol phospholipid hydrolysis than specific [3H]ketanserin binding. However, the effect of antidepressants was agonist-specific in that neither alpha-1 adrenoceptor nor muscarinic receptor stimulation were altered by acute or chronic treatment.
Kendall
D A
DA
Nahorski
S R
SR
D000345:Affinity Labels; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D006868:Hydrolysis; D007099:Imipramine / Q000494:pharmacology; D007488:Iprindole / Q000494:pharmacology; D007650:Ketanserin; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*
D000345:Affinity Labels; D000928:Antidepressive Agents; D010716:Phosphatidylinositols; D010880:Piperidines; D011985:Receptors, Serotonin; D010643:Phenoxybenzamine; D012701:Serotonin; D007488:Iprindole; D007650:Ketanserin; D007099:Imipramine