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PubMed · 8863849

5-hydroxytryptamine2C receptor activation inhibits 5-hydroxytryptamine1B-like receptor function via arachidonic acid metabolism.

K A Berg·S Maayani·W P Clarke
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Abstract

We previously reported that in Chinese hamster ovary (CHO) cells, 5-hydroxytryptamine (5-HT)1B-like (CHO/5-HT1B) receptor-mediated inhibition of forskolin-stimulated cAMP accumulation is inhibited by activation of transfected human 5-HT2C receptors but not 5-HT2A receptors. In the current study, we investigated the mechanism involved in the regulation of receptor-mediated inhibition of adenylyl cyclase as a means to further elucidate differences between the signal transduction cascades of the 5-HT2A and 5-HT2C receptor subtypes. Activation of 5-HT2C receptors with 5-HT or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane increased release of arachidonic acid via a phospholipase A2 (PLA2)-dependent mechanism. Incubation with (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 microM) abolished 5-carboxamidotryptamine (5 nM)-mediated inhibition of forskolin-stimulated cAMP accumulation, which was blocked by the PLA2 inhibitor mepacrine (100 microM) and the cyclooxygenase inhibitor indomethacin (2 microM). Furthermore, purinergic receptor-mediated PLA2 activation as well as direct activation of PLA2 with melittin reduced CHO/5-HT1B responsiveness. These data indicate that activation of the PLA2/arachidonic acid signaling cascade mediates 5-HT2C receptor regulation of the CHO/5-HT1B receptor pathway. Consistent with our previous report and in contrast to activation of 5-HT2C or purinergic receptors, activation of 5-HT2A receptors had no effect on CHO/5-HT1B receptor function, although 5-HT2A receptor-mediated activation of PLA2 was measured. Interestingly, purinergic receptor-mediated inhibition of CHO/5-HT1B receptor function was blocked when 5-HT2A receptors were activated simultaneously. These data suggest that the lack of 5-HT2A mediated regulation of CHO/5-HT1B receptors may be due to activation of a third pathway (in addition to PLC and PLA2 pathways), which results in the inhibition of the production or the actions of a cyclooxygenase-dependent arachidonic acid metabolite.

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AnimalsArachidonic AcidCHO CellsCricetinaeCyclic AMPCyclooxygenase InhibitorsEnzyme ActivationHumansIndomethacinPhospholipases APhospholipases A2Prostaglandin-Endoperoxide SynthasesReceptor, Serotonin, 5-HT2CReceptors, PurinergicReceptors, SerotoninSerotonin AntagonistsSerotonin Receptor AgonistsTransfectionJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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BibTeXRIS

K A Berg, S Maayani, W P Clarke. 1996. 5-hydroxytryptamine2C receptor activation inhibits 5-hydroxytryptamine1B-like receptor function via arachidonic acid metabolism.. https://pubmed.ncbi.nlm.nih.gov/8863849/

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