[(3)H]-serotonin release from bovine iris-ciliary body: pharmacology of prejunctional serotonin (5-HT(7)) autoreceptors

Exp Eye Res. 2001 Jul;73(1):59-67. doi: 10.1006/exer.2001.1012.

Abstract

In the present study, we investigated the pharmacological characteristics of electrically stimulated [(3)H]-serotonin release from mammalian iris-ciliary bodies. Isolated bovine and human iris-ciliary bodies were loaded with [(3)H]-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 [(3)H]-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 [(3)H]-serotonin release was calcium-dependent, tetrodotoxin-sensitive and was enhanced by serotonin (EC(50) = 200 n M) and 5-carboxmidotryptamine (EC(50) = 4 n M). The rank order of potency of agonists in enhancing field-stimulated [(3)H]-serotonin release was: 5-carboamidotryptamine > m-chlorophenylbiguanide > 2-methyl-5-hydroxytryptamine = 5-methoxy-dimethyltryptamine > serotonin > 5-methoxy-tryptamine > L-694,247 = alpha-methyl-5-hydroxytryptamine > CGS 12066A = 8-hydroxy-2-(di- n -propylamino)tetraline. Serotonin and m-chlorophenylbiguanide also enhanced electrically-evoked [(3)H]-serotonin release from human iris-ciliary bodies with EC(50)s of 3 microM and 30 n M, respectively. The pharmacological profile displayed by serotonin receptor agonists was supported by the potent antagonism of the serotonin-induced enhancement of [(3)H]-serotonin release by 5HT(7)receptor antagonists SB-258718 (IC(50) = 18.6 +/- 1.2 nM; n = 4) and mesulergine (IC(50) = 0.26 +/- 0.05 nM; n = 4). However, antagonists at 5HT(6)and 5HT(3)receptors exhibited a relatively weak blockade of serotonin induced enhancement of field-stimulated [(3)H]-serotonin release. These studies have shown the presence of functionally active prejunctional 5HT(7)autoreceptors regulating the release of [(3)H]-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Animals
  • Cattle
  • Ciliary Body / drug effects
  • Ciliary Body / metabolism*
  • Electric Stimulation
  • Humans
  • Iris / drug effects
  • Iris / metabolism*
  • Middle Aged
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Tritium / metabolism*

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Tritium
  • Serotonin