title: Antagonistic effects of CompB on orphanin FQ-induced colonic contractions in rats.
abstract: Orphanin FQ has been shown to stimulate colonic contraction without affecting upper gastrointestinal motility in rats. We studied whether a new putative orphanin FQ receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (CompB), has antagonistic effects on orphanin FQ-induced colonic contractions in vivo and in vitro in rats. Orphanin FQ-(1-17) and orphanin FQ-(1-13) caused contractions of the circular muscle of the distal colon in a concentration dependent manner (10(-10)-10(-6) M) in vitro. CompB (10(-7)-10(-6) M) caused a significant inhibition on orphanin FQ-(1-17) and orphanin FQ-(1-13)-induced contractions without affecting the spontaneous contractions. Orphanin FQ-(1-17) also caused contractions of the distal colon in vivo. ED(50) dose of orphanin FQ-(1-17) (400 pmol/kg)-induced contractions were significantly antagonized by CompB (30-300 nmol/kg) in a dose-dependent manner. In contrast, CompB had no inhibitory effects on dynorphin A-induced contractions in vivo and in vitro. These indicate that CompB is a selective orphanin FQ receptor antagonist of the rat colon.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Takehira
authors.initials: T
authors.lastname: Yamamura
authors.forename: Toku
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D018723:Bethanechol / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D001562:Benzimidazoles; D018723:Bethanechol; D004399:Dynorphins; D018721:Muscarinic Agonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D010880:Piperidines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C402921:J 113397; C000722285:Oprl1 protein, rat