Up-regulation of 5-HT2 receptors in the rat brain by repeated administration of SR 46349B, a selective 5-HT2 receptor antagonist
| Autor: | F. Oury-Donat, Christian Congy, David Shire, Monsif Bouaboula, Jacques Simiand, Philippe Soubrie, Pierre Casellas, Murielle Rinaldi-Carmona, Jean-Claude Breliere, Gérard Le Fur |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Agonist medicine.medical_specialty Ketanserin medicine.drug_class Molecular Sequence Data Ritanserin In Vitro Techniques Pharmacology Polymerase Chain Reaction Second Messenger Systems Rats Sprague-Dawley Phenols Inosine Monophosphate Internal medicine medicine Animals RNA Messenger Receptor 5-HT receptor Brain Chemistry Cerebral Cortex Base Sequence Chemistry 5-HT2 receptor Amphetamines Antagonist Receptor antagonist Rats Serotonin Receptor Agonists Up-Regulation Fluorobenzenes Blotting Southern Endocrinology Receptors Serotonin Serotonin Antagonists medicine.drug |
| Zdroj: | European Journal of Pharmacology: Molecular Pharmacology. 246:73-80 |
| ISSN: | 0922-4106 |
| DOI: | 10.1016/0922-4106(93)90012-x |
| Popis: | Chronic administration (twice a day for three days and on the morning of the fourth day) of SR 46349B (trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3-(2-fluoroph enyl)propen-1- yl]phenol hemifumarate) (10 mg/kg, orally), a selective 5-HT2 receptor antagonist, caused 24 h later a marked increase (+42%) of the maximum binding capacity of [3H]ketanserin in rat brain cortical membranes without change in its affinity constant. Further, administration of the 5-HT2 receptor agonist, (+/-)-DOI((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (1 mg/kg, i.p.), produced in chronic SR 46349B treated rats a significant increase in the amount of [3H]-inositol phosphate compared to corresponding controls. In addition, subacute administration of SR 46349B caused a 2-fold increase in the head-twitch response to (+/-)-DOI (0.5 mg/kg, i.p.). This enhanced response was blocked by an acute administration of ritanserin (6-(2-[4-[bis(4-fluorophenyl)methylene]-1-piperidinyl]ethyl]-7- methyl-5H-thiazolo[3,2-a]pyrimidin-5-one) (10 mg/kg). Finally, a significant enhancement (+29%) of 5-HT2 receptor mRNA levels was observed in the cortex. Taken together, these data showed that an up-regulation of 5-HT2 receptors occurred in rats following repeated treatment with a selective 5-HT2 receptor antagonist. The effects of SR 46349B on 5-HT2 receptors might implicate pre-translational regulation. |
| Databáze: | OpenAIRE |
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