Pharmacological characterization of the 5-HT1A, 5-HT2 and 5-HT3 receptors in the bovine ciliary muscle

Eur J Pharmacol. 2003 Mar 7;464(1):69-74. doi: 10.1016/s0014-2999(03)01320-7.

Abstract

We aimed to investigate the effects of serotonin (5-hydroxytryptamine, 5-HT) on the bovine ciliary muscle and subsequently to characterize and identify the subtypes of 5-HT receptors involved in the serotonin-evoked contractility muscle. The binding of [3H]ketanserin, [3H]granisetron and [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) was analyzed. All labelled compounds bound with high affinity to a single site in the membrane preparations studied. The affinity (K(d)) of the binding site was 7.5+/-1.2 nM for [3H]ketanserin, 6.9+/-0.8 nM for [3H]granisetron and 4.4+/-0.31 nM for [3H]8-OH-DPAT. The density of receptors (B(max)) was 1062+/-43.0 fmol/mg protein for [3H]ketanserin, 566+/-2.32 fmol/mg protein for [3H]granisetron and 205+/-4.63 fmol/mg protein for [3H]8-OH-DPAT. The serotonin-induced contraction appeared to be competitively antagonized by ketanserin (0.1, 1 and 10 microM) and ondansetron (0.1, 10 and 100 microM) which produced a pA(2) value of 8.5+/-0.12 and 8.0+/-0.19, respectively. 8-OH-DPAT and 5-carboxamidotryptamine (5-CT) proved to be completely ineffective. We conclude that serotonin induces bovine ciliary muscle contraction via 5-HT(2) and 5-HT(3) receptors while the 5-HT(1A) receptors, although present, do not mediate the contractile response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Binding, Competitive
  • Cattle
  • Cell Membrane / metabolism
  • Ciliary Body / drug effects*
  • Ciliary Body / metabolism
  • Ciliary Body / physiology
  • Dose-Response Relationship, Drug
  • Granisetron / metabolism
  • Granisetron / pharmacology
  • In Vitro Techniques
  • Ketanserin / metabolism
  • Ketanserin / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology
  • Ondansetron / pharmacology
  • Radioligand Assay
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT1
  • Receptors, Serotonin, 5-HT3
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Tritium

Substances

  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Tritium
  • Serotonin
  • Ondansetron
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Ketanserin
  • Granisetron