Inhibition of cyclooxygenase-2 and EP1 receptor antagonism reduces human colonic longitudinal muscle contractility in vitro.
We investigated the contribution of cyclo-oxygenase enzyme inhibition and prostamide agonism on human colonic contractility in vitro. The effects of the non-specific COX inhibitor diclofenac were compared against selective COX-2 inhibition via nimesulide, the prostanoid EP(1) receptor antagonist SC19220 or the prostaglandin prodrug/prostamide receptor agonist bimatoprost, on potency of contraction to acetylcholine in human colonic circular and longitudinal muscle strips. Pre-treatment with either nimesulide (10(-5)M) or diclofenac (10(-6)M) caused a significant decrease in the potency of acetylcholine-evoked longitudinal muscle contraction, but did not inhibit acetylcholine-evoked circular muscle contraction. Pre-treatment with the EP(1) receptor antagonist SC19220 (10(-5)M) similarly decreased cholinergic potency in longitudinal muscle, without influence on circular muscle contraction. The prostamide agonist bimatoprost (10(-6)M) increased basal circular and longitudinal muscle tone, but did not alter cholinergic potency in either muscle layer. In conclusion, colonic longitudinal muscle contraction is augmented by COX-2 activity, most likely via PGE(2) acting at EP(1) receptors. While colonic contraction is tonically modulated by bimatoprost, it does not share the same functional properties attributed to other endogenous COX-2 metabolites on colonic contractile function.
Smid
Scott D
SD
Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, Australia. scott.smid@adelaide.edu.au
Svensson
Karin M
KM
D000109:Acetylcholine / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000069580:Bimatoprost; D003008:Cloprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides / Q000494:pharmacology
D000577:Amides; D052246:Cyclooxygenase 2 Inhibitors; C545635:PTGER1 protein, human; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides; D004008:Diclofenac; D003008:Cloprostenol; D051546:Cyclooxygenase 2; D000109:Acetylcholine; D000069580:Bimatoprost; C012655:nimesulide