bimatoprost and anandamide

Endocannabinoids are protective in animal colitis models. As endocannabinoids also form novel prostaglandin ethanolamides (prostamides) via COX-2, we investigated the effects of prostamides and other COX-2 mediators on tissue damage in an ex vivo human mucosal explant colitis model. Healthy human colonic mucosae were incubated with pro-inflammatory cytokines TNF-α and IL-1β to elicit colitis-like tissue damage. The PGF-ethanolamide analogue, bimatoprost decreased colitis scores which were reversed by a prostamide-specific antagonist AGN 211334, but not the FP receptor antagonist AL-8810. PGF-ethanolamide and PGE-ethanolamide also reduced cytokine-evoked epithelial damage. Anandamide was protective in the explant colitis model; however COX-2 inhibition did not alter its effects, associated with a lack of COX-2 induction in explant mucosal tissue. These findings support an anti-inflammatory role for prostamides and endocannabinoids in the human colon.

Topics: Adult; Amides; Arachidonic Acids; Bimatoprost; Cloprostenol; Colitis; Colon, Sigmoid; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Endocannabinoids; Female; Humans; Immunohistochemistry; Interleukin-1beta; Male; Middle Aged; Oxazoles; Polyunsaturated Alkamides; Receptors, Prostaglandin; Sulfonamides; Tissue Culture Techniques; Tumor Necrosis Factor-alpha; Young Adult

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

Topics: Adult; Amides; Antihypertensive Agents; Arachidonic Acids; Bimatoprost; Cannabinoid Receptor Modulators; Ciliary Body; Cloprostenol; Dinoprost; Endocannabinoids; Humans; In Vitro Techniques; Isometric Contraction; Latanoprost; Lipids; Muscle, Smooth; Piperidines; Polyunsaturated Alkamides; Prostaglandins F, Synthetic; Pyrazoles; Receptor, Cannabinoid, CB1; Receptors, Prostaglandin; Rimonabant; Travoprost