Serotonin-2B/2C Receptors Mediate Bovine Ciliary Muscle Contraction: Role in Intraocular Pressure Regulation.

PURPOSE: To study the pharmacological profile of the serotonin (5-hydroxytryptamine [5-HT]) receptor subtype mediating contractions in bovine isolated ciliary muscles.

METHODS: Ciliary muscle strips were isolated from bovine eyeballs and mounted in organ baths containing aerated (95% O2 , 5% CO2 ) Krebs buffer solution maintained at 37°C. Each muscle strip was attached at 1 end to a Grass Force-displacement Transducer connected to a Polyview Computer System for recording changes in isometric tension. After an equilibration period, ciliary muscle strips were exposed to selective agonists and antagonists of 5-HT receptors.

RESULTS: Both selective and nonselective agonists for 5-HT produced concentration-dependent contractions of isolated ciliary muscles with the following rank order of potency: BW723C86>α-methyl-5-HT>MK-212>8-hydroxy-DPAT>quipazine>R-DOI>5-HT>tryptamine. The selective 5-HT2 receptor antagonists, M-100907 (5-HT2A ), RS-127445 (5-HT2B ), and RS-102221 (5-HT2C ), produced noncompetitive inhibition of the contractile effects of selective agonists yielding antagonist potency (pKB ) values of 251 ± 27.2 nM (n = 4), 52.5 ± 6.3 nM (n = 4), and 79.4 ± 9.5 nM (n = 4), respectively.

CONCLUSION: On the basis of the profile of activity of selective agonists and antagonists, we conclude that the 5-HT2B and 5-HT2C receptor subtypes appear to be the predominant serotonin receptors that mediate the contractile action of this amine in bovine isolated ciliary muscles.