Evidence for the involvement of cannabinoid CB1 receptors in the bimatoprost-induced contractions on the human isolated ciliary muscle.
OBJECTIVE
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.
Romano
Maria Rosaria
MR
Department of Pharmacobiology, Section of Pharmacology, University of Bari, Bari, Italy.
Lograno
Marcello Diego
MD
D000328:Adult; D000577:Amides / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D000069580:Bimatoprost; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D063388:Endocannabinoids; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D000077338:Latanoprost; D008055:Lipids / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D000077285:Rimonabant; D000069557:Travoprost
C518977:AL 8810 ethylamide; D000577:Amides; D000959:Antihypertensive Agents; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D008055:Lipids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011461:Prostaglandins F, Synthetic; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011982:Receptors, Prostaglandin; D003008:Cloprostenol; D000077338:Latanoprost; D015237:Dinoprost; D000069580:Bimatoprost; D000077285:Rimonabant; C078814:anandamide; D000069557:Travoprost