RGD Reference Report - DOI, an agonist of 5-HT2A/2C serotonin receptor, alters the expression of cyclooxygenase-2 in the rat parietal cortex. - Rat Genome Database

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DOI, an agonist of 5-HT2A/2C serotonin receptor, alters the expression of cyclooxygenase-2 in the rat parietal cortex.

Authors: Mackowiak, M  Chocyk, A  Sanak, M  Czyrak, A  Fijal, K  Wedzony, K 
Citation: Mackowiak M, etal., J Physiol Pharmacol 2002 Sep;53(3):395-407.
RGD ID: 729238
Pubmed: PMID:12369737   (View Abstract at PubMed)

The hallucinogenic effect of DOI, serotonin 5-HT2A/2C receptor agonist, is known to be associated with the activation of cortical 5-HT2 receptors. However, the effect of DOI on excitability of cortical neurons and their subsequent function is still not quite understood. Previous immunohistochemical studies using Fos proteins expression as a marker of neuronal activity showed the involvement of arachidonic acid cascade, particularly cyclooxygenase metabolic pathway, in DOI-induced Fos proteins expression in the rat parietal cortex. DOI increases arachidonic acid release which is transformed itself via acceleration of cyclooxygenase metabolic pathway to biologically active metabolites, such as prostaglandins and thromboxanes. Since cyclooxygenase-2 (COX-2) expression correlates with neuronal activity, it was of interest to investigate whether DOI is capable of influencing the level of COX-2 protein and mRNA expression in the rat parietal cortex. It was observed that neurons which were positive for 5-HT2A receptors showed constitutive COX-2 immunoreactivity. It was found further, that COX-2 protein level was increased at 1 h, and returned to the control level at 3 and 6 h after DOI (5 mg/kg) administration. In contrast, DOI decreased the COX-2 mRNA expression at all tested time points (1 h, 3h and 6h after DOI treatment). The obtained results further support the suggestion that COX-2 activation and possibly arachidonic acid metabolites generated by COX-2 may be considered as important mediators of functional responses generated by activation of cortical 5-HT2A/2C receptors.

Objects referenced in this article
Gene Htr2a 5-hydroxytryptamine receptor 2A Rattus norvegicus
Gene Htr2c 5-hydroxytryptamine receptor 2C Rattus norvegicus
Gene Ptgs2 prostaglandin-endoperoxide synthase 2 Rattus norvegicus

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