The effect of nociceptin, an endogenous ligand for the ORL1 receptor, on rat colonic contraction and transit.
To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.
Taniguchi
H
H
Discovery Research Laboratory, Tanabe Seiyaku, Toda, Saitama, Japan. h-tani@tanabe.co.jp
Yomota
E
E
Nogi
K
K
Onoda
Y
Y
Ikezawa
K
K
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005772:Gastrointestinal Transit / Q000187:drug effects*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D008024:Ligands; D009020:Morphine; D009479:Neuropeptides; D018847:Opioid Peptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); C000722285:Oprl1 protein, rat