Activity of mu- and delta-opioid agonists in vas deferens from mice deficient in MOR gene.
1. Mice lacking the mu-opioid receptor have been recently generated. Centrally mediated responses of mu-opioid agonists are suppressed whereas some of the delta-opioid responses are preserved in these mutant mice. 2. The vas deferens bioassay has been used in this study to investigate the functional activity at a peripheral level of mu- and delta-opioid agonists in mice lacking mu-opioid receptors. 3. The different mu-opioid agonists evaluated, morphine, DAMGO, dermorphin and [Lys(7)]-dermorphin produced an inhibitory response in vas deferens from wild-type mice but had no relevant activity on vas deferens from mutant mice. 4. The selective delta-opioid agonists DPDPE, BUBU, deltorphin I, deltorphin II and [D-Met(2)]-deltorphin induced inhibitory effects in vas deferens from both wild-type and mutant mice. However, the biological activities of these ligands were slightly reduced in preparations from mutant mice. The inhibitory responses of all these delta-opioid agonists were prevented by the administration of the selective delta-opioid antagonist naltrindole. 5. These data indicate that delta-opioid agonists, but not mu-opioid agonists, are biologically active in vas deferens from mice lacking mu-opioid receptors. The decreased response of delta-agonists in mutant mice suggests that some cooperativity may exist between mu- and delta-opioid receptors in these vas deferens preparations.
Laboratori de Neurofarmacologia, Facultat de Ciences de la Salut i de la Vida, Universitat Pompeu Fabra, c/Dr Aiguader 80, 08003 Barcelona, Spain. rafael.maldonado@cexs.upf.es
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Maldonado
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Severini
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Matthes
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Kieffer
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Melchiorri
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Negri
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005260:Female; D005838:Genotype; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000172:deficiency / Q000235:genetics; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C091812:dermorphin, Lys(7)-; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C062971:tyrosyl-seryl(O-t-butyl)-glycyl-phenylalanyl-leucyl-threonine(O-t-butyl); C060208:deltorphin I, Ala(2)-; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole