Evidence for the involvement of cannabinoid CB1 receptors in the bimatoprost-induced contractions on the human isolated ciliary muscle

Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3677-82. doi: 10.1167/iovs.06-0896.

Abstract

Purpose: To evaluate the bimatoprost effects in the isolated human ciliary muscle and to assess how these response can be modulated by AL8810 and SR141716A.

Methods: In a myograph system (isometric force measurement), ciliary muscles were exposed cumulatively to PGF(2alpha), latanoprost, travoprost, bimatoprost, and anandamide (0.1 nM-10 microM). Experiments were also conducted in the presence of AL8810 (FP receptor antagonist; 100 nM) or SR141716A (CB(1) receptor antagonist; 10-100 nM). Contractions were expressed as the percentage of 10 microM carbachol-induced contractions.

Results: In quiescent tissues, concentration-response curves for bimatoprost, anandamide, PGF(2alpha,) latanoprost, and travoprost were constructed. Bimatoprost showed an important contractile effect on isolated human ciliary muscle strips (E(max) = 125% +/- 0.09%); the maximal effect was higher than that obtained with carbachol. Contractions were inhibited by SR141716A (10 and 100 nM) and AL8810 (100 nM).

Conclusions: This study showed evidence of direct interaction of bimatoprost with the contractility of the human ciliary muscle through interaction with cannabinoid CB(1) receptor and prostanoid FP receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amides / pharmacology*
  • Antihypertensive Agents / pharmacology*
  • Arachidonic Acids / pharmacology
  • Bimatoprost
  • Cannabinoid Receptor Modulators / pharmacology
  • Ciliary Body / cytology
  • Ciliary Body / drug effects*
  • Ciliary Body / physiology
  • Cloprostenol / analogs & derivatives*
  • Cloprostenol / pharmacology
  • Dinoprost / analogs & derivatives
  • Dinoprost / pharmacology
  • Endocannabinoids
  • Humans
  • In Vitro Techniques
  • Isometric Contraction / drug effects*
  • Isometric Contraction / physiology
  • Latanoprost
  • Lipids / pharmacology*
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / pharmacology
  • Prostaglandins F, Synthetic / pharmacology
  • Pyrazoles / pharmacology
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / physiology
  • Receptors, Prostaglandin / agonists
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / physiology
  • Rimonabant
  • Travoprost

Substances

  • AL 8810 ethylamide
  • Amides
  • Antihypertensive Agents
  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Lipids
  • Piperidines
  • Polyunsaturated Alkamides
  • Prostaglandins F, Synthetic
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptors, Prostaglandin
  • Cloprostenol
  • Latanoprost
  • Dinoprost
  • Bimatoprost
  • Rimonabant
  • anandamide
  • Travoprost