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Serotonergic, 5-HT2, Receptor-Mediated phosphoinositide Turnover and Mobilization of Calcium in Cultured Rat Retinal Pigment Epithelium Cells

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Osborne, NN, FitzGibbon, F, Nash, M, Liu, NP, Leslie, R and Cholewinski, A (1993) Serotonergic, 5-HT2, Receptor-Mediated phosphoinositide Turnover and Mobilization of Calcium in Cultured Rat Retinal Pigment Epithelium Cells. Vision Research, 33 (16). pp. 2171-2179. [Journal article]

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URL: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0W-484M7ST-1CD&_user=4008657&_coverDate=11%2F30%2F1993&_alid=1459464587&_rdoc=9&_fmt=high&_orig=search&_origin=search&_zone=rslt_list_item&_cdi=4873&_sort=r&_st=13&_docanchor=&view=c&_ct=16&_acct

DOI: 10.1016/0042-6989(93)90097-G

Abstract

Cultured rat retinal pigment epithelium cells are shown to contain serotonergic, 5-HT2, receptors associated with phosphoinositide turnover and mobilization of intracellular calcium. Serotonin at a concentration of 10 μM induced a 2.5-fold increase in [3H]-inositol phosphates (more than 75% is in the form of [3H]-inositol-1-phosphate) accumulation within 30 min in cells preincubated in [3H]-myo-inositol and exposed to 5 mM lithium chloride. The EC50 value of serotonin was approx. 0.9 μM and the saturation concentration was 100 μM. Serotonin analogues like tryptamine, 5-methoxytryptamine, α-methyl-serotonin and the 5-HT2 agonists quipazine and DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane) all stimulated InsPs accumulation to some degree. Carbachol, noradrenaline, isoproterenol, dopamine, tryptophan, 5-hydroxytryptophan, 8-hydroxy-2 (di-n-propyl-amino) tetralin, 2-methyl-serotonin and NEC A (5′-[N-ethyl]-carboxamidoadenosine) were inactive. The serotonin-induced response was blocked most effectively by ketanserin and methysergide but not by 5-HT3 or 5-HT1, antagonists. The serotonin response was attenuated by the active phorbol ester, 4β-phorbol 12-myristate 13-acetate and this was attenuated by the non-selective protein kinase C inhibitor, staurosporine. Pertussis toxin failed to influence the serotonin-mediated phosphoinositide turnover. Addition of serotonin to cultures loaded with Fura-2 showed a transient increase in calcium concentrations in most of the cells. This change in calcium was independent of external calcium and the serotonin response was attenuated by ketanserin but not by the 5-HT3 antagonist granisetron. These studies provide clear evidence for the presence of 5-HT2 receptors, coupled to phosphoinositide metabolism and mobilization of calcium, on cultured rat retinal pigment epithelium cells.

Item Type:Journal article
Keywords:5-HT2 receptors;phosphoinositides;calcium;retinal pigmnt cells
Faculties and Schools:Faculty of Computing & Engineering
Faculty of Computing & Engineering > School of Engineering
Research Institutes and Groups:Engineering Research Institute
Engineering Research Institute > Nanotechnology & Integrated BioEngineering Centre (NIBEC)
ID Code:15632
Deposited By:Mr Francis FitzGibbon
Deposited On:16 Sep 2010 14:44
Last Modified:04 Oct 2010 12:21

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