Effects of subchronic pretreatment with D-fenfluramine or p-chloroamphetamine on [3H]inositolmonophosphate accumulation in rat cortical miniprisms. 1994

A Erfurth, and A M Gardier, and E Ribeiro, and R J Wurtman
Department of Brain and Cognitive Sciences, Wurtman Lab., Massachusetts Institute of Technology, Cambridge 02139.

Phosphatidylinositol (PI) breakdown in rat cerebral cortex is stimulated by serotonin (5-HT), acting via 5-HT2 and possibly 5-HT3 receptors and by acetylcholine or carbachol, acting via muscarinic M1 and M3 receptors. Serotoninergic neurons have been described as tonically inhibiting cortical acetylcholine release. We studied the effects of subchronic pretreatment with high doses of D-fenfluramine (10 mg/kg, i.p., daily for 4 days), which releases 5-HT and blocks its reuptake, on 5-HT-and carbachol-stimulated PI breakdown, as measured by [3H]inositolmonophosphate ([3H]IP1) accumulation in cortical miniprisms. This pretreatment decreased 5-HT-stimulated [3H]IP1 accumulation, suggesting that a prolonged increase of 5-HT in the synaptic cleft reduces the activity of the transducing system used by postsynaptic 5-HT receptors. Carbachol-stimulated PI breakdown was unaltered by pretreatment with D-fenfluramine. Pretreatment with a single dose of p-chloroamphetamine (5 mg/kg), a serotoninergic neurotoxin, which depleted cortical 5-HT by 85%, did not change [3H]IP1 accumulation after stimulation by 5-HT or by the muscarinic agonist carbachol. Subchronic pretreatment, which depleted cortical 5-HT by 90%, decreased both 5-HT- and carbachol-stimulated [3H]IP1 accumulation. The mechanism by which p-chloroamphetamine, but not D-fenfluramine, diminishes the PI response to carbachol might involve impairment of the tonic serotoninergic inhibition of acetylcholine release.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007295 Inositol Phosphates Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID. Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D008297 Male Males
D010133 p-Chloroamphetamine Chlorinated analog of AMPHETAMINE. Potent neurotoxin that causes release and eventually depletion of serotonin in the CNS. It is used as a research tool. p-Chloramphetamine,para-Chloroamphetamine,LY-121860,Ly-123362,Parachloroamphetamine,LY 121860,LY121860,Ly 123362,Ly123362,p Chloramphetamine,p Chloroamphetamine,para Chloroamphetamine
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005277 Fenfluramine A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. Fintepla,Fenfluramine Hydrochloride,Fenfluramine Hydrochloride, (+-)-Isomer,Fenfluramine Hydrochloride, R-Isomer,Fenfluramine, (+-)-Isomer,Fenfluramine, R-Isomer,Isomeride,Pondimin,Fenfluramine Hydrochloride, R Isomer,Fenfluramine, R Isomer,Hydrochloride, Fenfluramine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine

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