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. Central ly 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 a nd [Lys(7)]dermorphin produced an inhibitory response in vas deferens from wild-type mice but had no relevant activity on vas deferens from mutant mic e. 4 The selective delta-opioid agonists DPDPE, BUBU, deltorphin I, deltorphin II and [D-Met(2)]deltorphin induced inhibitory effects in vas deferens fro m both wild-type and mutant mice. However, the biological activities of the se ligands were slightly reduced in preparations from mutant mice. The inhi bitory responses of all these delta-opioid agonists were prevented by the a dministration of the selective delta-opioid antagonist naltrindole. 5 These data indicate that delta-opioid agonists, but not mu-opioid agonist s, are biologically active in vas deferens from mice lacking mu-opioid rece ptors. The decreased response of delta-agonists in mutant mice suggests tha t some cooperativity may exist between mu- and delta-opioid receptors in th ese vas deferens preparations.