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N.A. Sharif, C.R. Kelly, J.Y. Crider, M. Senchyna; Human Ciliary Muscle and Trabecular Meshwork Cells Express Functional Serotonin-2 (5-HT2) Receptors Coupled to Phosphoinositide Turnover and [Ca2+]i Mobilization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2084.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Serotonin (5-HT) is an endogenous biogenic amine. Serotonergic innervation of the iris-ciliary body and the detection of 5-HT in the aqueous humor suggests a role for 5-HT in aqueous humor dynamics. We sought to demonstrate the existence of 5HT2 receptor mRNAs and functionally coupled 5-HT2 receptors in human ciliary muscle (h-CM) and human trabecular meshwork (h-TM) cells. Methods: Detection of mRNAs for 5-HT2A-C receptors in h-TM cells (8 donors) and in human ciliary bodies (h-CBs;6 donors) was performed using RT-PCR procedures. Phosphoinositide (PI) turnover and mobilization of intracellular Ca2+ ([Ca2+]i) in h-CM and h-TM cells was determined using standard techniques. Results: RT-PCR analysis revealed the presence of mRNAs for human 5-HT2A and 5-HT2B (but not 5-HT2C) receptors in h-TM cells. Human CBs contained mRNAs for 5-HT2A-C receptors. 5-HT induced PI turnover (h-CM EC50 = 106 ± 21 nM; h-TM EC50 = 413 ± 137 nM) and mobilized [Ca2+]i (EC50 = 770 nM in h-CM and EC50 = 61 nM in h-TM) in these cell types. Similarly, α-methyl-5-HT was a potent agonist in h-CM (EC50= 84 ± 7 nM) and in h-TM (EC50 = 250 ± 73 nM) cell PI assays. MDL-100907, a 5-HT2A receptor antagonist, potently antagonized (IC50 = 0.6 ± 0.29 nM; n = 4) 5-HT2 agonist-induced PI turnover in h-TM cells. Conclusions: These studies demonstrated the presence of the mRNAs for 5-HT2 receptors in h-TM cells and h-CB tissue. Since 5-HT and α-methyl-5-HT stimulated PI turnover and mobilized [Ca2+]i, that could be antagonized by MDL-100907, the presence of functionally coupled 5-HT2 receptors in the h-TM and h-CM cells was confirmed. These data suggest a role of 5-HT2 receptors in modulating aqueous humor dynamics and intraocular pressure.
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