[3H]-Serotonin release from bovine iris-ciliary body: Pharmacology of prejunctional serotonin (5-HT7) autoreceptors

Lydia C. Harris, S. Olubusayo Awe, Catherine A. Opere, Angela M. LeDay, Sunny E. Ohia, Najam A. Sharif

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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 = 200 nM) and 5-carboxmidotryptamine (EC50 = 4 nM). 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 3 μM and 30 nM, 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 5HT7 receptor antagonists SB-258718 (IC50 = 18.6 ± 1.2 nM; n = 4) and mesulergine (IC50 = 0.26 ± 0.05 nM; n = 4). However, antagonists at 5HT6 and 5HT3 receptors 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 5HT7 autoreceptors 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.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalExperimental Eye Research
Volume73
Issue number1
DOIs
StatePublished - Jan 1 2001

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All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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