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Naj Sharif, Madura Kulkarni-Chitnis, Ya Fatou Njie-Mbye, Sunny E Ohia; Pharmacological Evidence for Serotonin-2B Receptor-Mediated Bovine Ciliary Muscle Contraction.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3024.
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© ARVO (1962-2015); The Authors (2016-present)
To use receptor-selective agonists and antagonists to determine the pharmacological identity of receptors for serotonin (5-hydroxytryptamine, 5HT) involved in contracting bovine ciliary muscle (CM) in vitro.
Standard equipment and procedures were utilized to record longitudnal isometric tension responses of CM strips (4-5 mm) mounted in 25mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5HT agonists to define their relative potencies. Schild analyses of data from multiple C-R curves generated in presence and absence of receptor-selective antagonists (3 concentrations) yielded the antagonist potencies (-log concentration of antagonist required to shift the C-R to the right by 2-fold, pA2; Br J Pharmacol. Chemother. 14: 45-48, 1959).
Bovine CM strips contracted in response to various serotonergic agonists in a differential and concentration-dependent manner. Amongst the most potent agents were the 5HT2B-receptor-selective (BW723C86; EC50 = 0.5 ± 0.1 nM, n = 10) and 5HT2C-receptor-selective (MK-212; EC50 = 4.1 ± 1.4 nM, n = 11) agonists with the 5HT2A-receptor-selective agonist R-DOI (EC50 = 190 ± 70 nM, n = 8) being substantially less potent. Other 5HT agonists exhibited a range of potencies: 8-hydroxy-tryptamine (5HT1A; EC50 = 130 nM), quipazine (5HT3; EC50 = 170 nM), 5HT (EC50 = 2390 nM). The effects of receptor-selective agonists were most potently blocked by the antagonists RS-127445 (5HT2B-selective; pA2 = 7.7 ± 0.57; i.e. 19.9 nM) and RS-102221 (5HT2C-selective; pA2 = 7.1 ± 0.05; i.e. 79.4 nM), and least by M-100907 (5HT2A-receptor-selective antagonist, pA2 = 6.6 ± 0.6; i.e. 251 nM).
These data indicate that 5HT2B receptors are predominantly involved in mediating the contraction of bovine CM, with lesser contributions from 5HT2C, 5HT2A, 5HT1A and 5HT3 receptors. These findings differed from those previously reported for isolated primary human CM and trabecular meshwork cell responses (PI turnover; [Ca2+]i mobilization) induced by serotonergic agents where 5HT2A receptors were predominantly involved; this correlating with IOP reduction induced by 5HT2A agonists in vivo. These data further illustrate the species differences in functional responses triggered by serotonin in cells and tissues involved in aqueous humor dynamics and IOP regulation.
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