The presence of serotonin (5-HT1) receptors negatively coupled to adenylate cyclase in rabbit and human iris-ciliary processes

Exp Eye Res. 1993 Aug;57(2):209-16. doi: 10.1006/exer.1993.1116.

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) reduces forskolin-induced stimulation of cyclic AMP in rabbit iris-ciliary body (ICB) homogenates. The effect is dose dependent and can be mimicked by a number of 5-HT1 receptor agonists including 5-carboxamidotryptamine (5-CT) and RU 24969 [5-methoxy-3-(1,2,3,6, tetrahydro-4-pyridinyl)-1-indole]. The inhibitory effects of 5-CT and the 5-HT1A selective agent 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) on forskolin stimulated adenylate cyclase activity are greater in isolated ciliary processes than in the iris musculature. Spiperone and propranolol significantly antagonize the action of 5-CT in the iris-ciliary body, while ketanserin (5-HT2 antagonist) and ICS 205930 (5-HT3/4 blocker) were without influence, indicating the presence of the 5-HT1A subtype of receptor. Studies carried out on human ICB homogenates also suggest the presence of 5-HT1A-like receptors, although these receptors are not identical to those in rabbit. Similarities include dose-dependent decreases in cAMP levels stimulated by forskolin elicited by 1-(3-chlorophenyl) piperazine (mCPP), 5-CT and 8-OH-DPAT. Moreover, the inhibitory effect of 5-CT can also be significantly reduced by the 5-HT1 receptor antagonist, propranolol. However, unlike the case of rabbit tissue, spiperone was ineffective in abolishing the 5-CT response in human ICB homogenates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Ciliary Body / metabolism*
  • Colforsin / pharmacology
  • Cyclic AMP / biosynthesis
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Iris / metabolism*
  • Rabbits
  • Receptors, Serotonin / metabolism*
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology

Substances

  • Receptors, Serotonin
  • Colforsin
  • Serotonin
  • 5-carboxamidotryptamine
  • Cyclic AMP
  • Adenylyl Cyclases