Document Detail

Serotonin-2 (5-HT2) receptor-mediated signal transduction in human ciliary muscle cells: role in ocular hypotension.
MedLine Citation:
PMID:  17238805     Owner:  NLM     Status:  MEDLINE    
PURPOSE AND METHODS: The aim of this study was to characterize the serotonin (5-hydroxytryptamine; 5-HT) receptors that mediate phosphoinositide (PI) hydrolysis and intracellular Ca2+ ([Ca2+]i) mobilization in isolated cells of human ciliary muscle (h-CM) from multiple donors using a variety of agonists and antagonists. An additional aim was to visualize the mRNAs and receptor binding sites for 5-HT2 receptors in human ciliary body (h-CB), CM, and other tissues by reverse transcriptase polymerase chain reaction and quantitative autoradiography techniques, respectively, and to correlate with ocular hypotensive activity of such compounds. RESULTS: CBs isolated from several donor eyes revealed the presence of 5-HT(2A2C) receptor mRNAs. [3H]-5-HT and [3H]-ketanserin autoradiography on sections of human eyes revealed a high density of 5-HT2 receptor binding sites in the iris, ciliary epithelium, and longitudinal CM. In isolated h-CM cells, the agonists alpha-methyl-5-HT (EC50=63+/-17 nM), 5-HT (EC50=85+/-16 nM), (R)-DOI (EC50=165+/-47 nM), and 5-methoxy alpha-methyl tryptamine (EC50=1200+/-270 nM) differentially stimulated PI turnover. These agonists also mobilized [Ca2+]i in h-CM cells with the following potencies (EC50s): 5-methoxy-tryptamine=42+/-11 nM; alpha-methyl-5-HT=36+/-11 nM; (R)-DOI=120 nM; 5-HT=130+/-36 nM; MK-212=470 nM; mCPP>1 microM; BW723C86=1766 nM. The agonist-induced [Ca2+]i mobilization in h-CM cells was potently blocked by the 5-HT2A-selective antagonist M-100907 (IC50=1.2+/-0.4 nM) but less potently by the antagonists for 5-HT2B (RS-127445, IC50>10 microM) and 5-HT2C (RS-102221, IC50=5.8+/-2.3 microM) receptors. CONCLUSIONS: In conclusion, h-CB, h-CM, and CM cells express mRNAs and proteins for 5-HT2 receptor subtypes, of which the predominant functionally active subtype is the 5-HT2A receptor, as defined by agonist and antagonist activities. These receptors may be responsible for mediating the intraocular pressure reduction observed in recent literature with a number of 5-HT2 agonists, such as (R)-DOI, alpha-methyl-5HT, and AL-34662.
Najam A Sharif; Curtis R Kelly; Julie Y Crider; Terry L Davis
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics     Volume:  22     ISSN:  1080-7683     ISO Abbreviation:  J Ocul Pharmacol Ther     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2007-01-22     Completed Date:  2007-02-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9511091     Medline TA:  J Ocul Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  389-401     Citation Subset:  IM    
Ophthalmology Discovery Research, Alcon Research, Ltd., Fort Worth, TX 76134-2099, USA.
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MeSH Terms
Aged, 80 and over
Binding Sites
Calcium / metabolism
Cell Culture Techniques
Cells, Cultured
Ciliary Body / cytology,  metabolism*
Middle Aged
Muscle Cells / metabolism*
Ocular Hypertension* / etiology,  metabolism
Protein Binding
Receptors, Serotonin, 5-HT2 / biosynthesis*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Reg. No./Substance:
0/Receptors, Serotonin, 5-HT2; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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