Abstract
In the present study, we investigated the pharmacological characteristics of electrically stimulated [3H]-serotonin release from mammalian iris-ciliary bodies. Isolated bovine and human iris-ciliary bodies were loaded with [3H]-serotonin, superfused with Krebs buffer solution and then stimulated with trains of 300 direct current (d.c.) pulses to initiate the release of the transmitter. The modification of this [3H]-serotonin release process by various serotonergic agonists and antagonists was studied in order to define the pharmacology of serotonin receptor(s) present in the iris-ciliary body. In bovine iris-ciliary body, electrically-evoked [3H]-serotonin release was calcium-dependent, tetrodotoxin-sensitive and was enhanced by serotonin (EC50=200n M) and 5-carboxmidotryptamine (EC50=4n M). The rank order of potency of agonists in enhancing field-stimulated [3H]-serotonin release was: 5-carboamidotryptamine>m-chlorophenylbiguanide>2-methyl-5-hydroxytryptamine=5-methoxy-dimethyltryptamine>serotonin>5-methoxy-tryptamine>L-694,247=α-methyl-5-hydroxytryptamine>CGS 12066A=8-hydroxy-2-(di- n -propylamino)tetraline. Serotonin and m-chlorophenylbiguanide also enhanced electrically-evoked [3H]-serotonin release from human iris-ciliary bodies with EC50s of 3μM and 30n M, respectively. The pharmacological profile displayed by serotonin receptor agonists was supported by the potent antagonism of the serotonin-induced enhancement of [3H]-serotonin release by 5HT7receptor antagonists SB-258718 (IC50=18.6±1.2n M;n=4) and mesulergine (IC50=0.26±0.05n M;n=4). However, antagonists at 5HT6and 5HT3receptors exhibited a relatively weak blockade of serotonin induced enhancement of field-stimulated [3H]-serotonin release. These studies have shown the presence of functionally active prejunctional 5HT7autoreceptors regulating the release of [3H]-serotonin from bovine iris-ciliary bodies. Excitatory prejunctional 5-HT autoreceptors also exist in human iris-ciliary bodies. It is possible that these serotonin autoreceptors may have relevance to the regulation of aqueous humor dynamics in the anterior uvea.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call