5-HYDROXYTRYPTAMINE-STIMULATED INOSITOL PHOSPHOLIPID HYDROLYSIS IN RAT CEREBRAL-CORTEX SLICES - PHARMACOLOGICAL CHARACTERIZATION AND EFFECTS OF ANTIDEPRESSANTS
- 1 January 1985
- journal article
- research article
- Vol. 233 (2), 473-479
Abstract
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.This publication has 17 references indexed in Scilit:
- Serotonin‐Elicited Amplification of Adenylate Cyclase Activity in Hippocampal Membranes from Adult RatJournal of Neurochemistry, 1983
- Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glandsBiochemical Journal, 1982
- [H-3]-LABELED KETANSERIN (R 41 468), A SELECTIVE H-3-LABELED LIGAND FOR SEROTONIN-2 RECEPTOR-BINDING SITES - BINDING-PROPERTIES, BRAIN DISTRIBUTION, AND FUNCTIONAL-ROLE1982
- Two Distinct Central Serotonin Receptors with Different Physiological FunctionsScience, 1981
- Discrimination of Multiple [3H]5‐Hydroxytryptamine Binding Sites by the Neuroleptic Spiperone in Rat BrainJournal of Neurochemistry, 1981
- Optimal Conditions for [3H]Apomorphine Binding and Anomalous Equilibrium Binding of [3H]Apomorphine and [3H]Spiperone to Rat Striatal Membranes: Involvement of Surface Phenomena Versus Multiple Binding SitesJournal of Neurochemistry, 1981
- Long-Term Antidepressant Treatment Decreases Spiroperidol-Labeled Serotonin Receptor BindingScience, 1980
- Serotonin-sensitive adenylate cyclase and [3]serotonin binding sites in the CNS of the rat—IBiochemical Pharmacology, 1980
- MULTIPLE SEROTONIN RECEPTORS - DIFFERENTIAL BINDING OF [5-HYDROXYTRYPTAMINE-H-3, [LYSERGIC-H-3 ACID DIETHYLAMIDE AND [H-3]SPIROPERIDOL1979
- PHENOXYBENZAMINE ANTAGONISM OF TRYPTAMINES THEIR INDENE ISOSTERES AND 5-HYDROXYTRYPTAMINE IN RAT STOMACH FUNDUS PREPARATION1968