Activity of mu‐ and delta‐opioid agonists in vas deferens from mice deficient in MOR gene

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. 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. 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. 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. 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.British Journal of Pharmacology (2001) 132 , 1485–1492; doi: 10.1038/sj.bjp.0703966