Different motor actions of dynorphins and nonpeptide kappa opioid receptor agonists in the isolated rat colon.
Dynorphin 1-17 has been suggested to be the endogenous ligand for kappa opioid receptors. In this study motor effects of dynorphin 1-17, its N-terminal fragments d-Pen2,d-Pen5-enkephalin (DPDPE) and d-Ser2-[Leu5]enkephalin-Thr (DSLET) without or with pretreatment with naloxone, (-)-2-(furylmethyl)-noretacocine (Mr 2266) or tetrodotoxin (TTX) on the isolated rat colon were compared with those of nonpeptide kappa opioid receptor agonists. Intraluminal pressure changes were measured by perfusion manometry in preparations maintained in a standard organ bath. Dynorphin 1-17, 1-9, 1-8, 1-6, [Leu5]enkephalin, DPDPE and DSLET dose dependently stimulated the tone in the proximal, middle and distal colon with the maximum response at 10(-6) to 10(-5) M. The stimulation produced by Tyr-Gly-Gly-Phe and Tyr-Gly-Gly was 60 and 600 times less potent, respectively. Concentrations of 10(-10) to 10(-6) M des-Tyr1-[Leu5]enkephalin, dynorphin 3-13, 6-17, 1-methyl-2-(3-thienylcarbonyl)-amino-ethyl-5-(2-fluorophenyl)-H-2,3 dihydro-1,4-benzodiazepine, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl) cyclohexyl)-benzene- acetamide-methane sulfonate and (5a,7a,8B)-(-)-N-methyl-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)-dec-8- yl) benzeneacet-amide produced no changes in motor activity of the rat colon. Only doses exceeding 10(-6) M of the latter three substances stimulated colonic tone. This action was inhibited neither by naloxone nor by Mr 2266. In contrast, the stimulation by dynorphin 1-17 and 1-6 was inhibited to a greater extent by naloxone than by Mr 2266.(ABSTRACT TRUNCATED AT 250 WORDS)
Scheurer
U
U
Gastrointestinal Unit, University Hospital, Inselspital, Bern, Switzerland.
Wenger
F
F
Caliezi
A
A
Drack
E
E
Varga
L
L
Halter
F
F
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044482:Benzeneacetamides; D001569:Benzodiazepines / Q000494:pharmacology*; D001575:Benzomorphans / Q000494:pharmacology; D003106:Colon; D004232:Diuretics / Q000494:pharmacology*; D004399:Dynorphins / Q000031:analogs & derivatives / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011312:Pressure; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa
D000700:Analgesics; D000959:Antihypertensive Agents; D044482:Benzeneacetamides; D001575:Benzomorphans; D004232:Diuretics; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D001569:Benzodiazepines; D009270:Naloxone; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C045444:U 69593; C035470:tifluadom