The choice of opioid receptor subtype in isolated preparations by dynorphins.

The choice of opioid receptor subtype by dynorphins was studied in isolated preparations. Both dynorphin-(1-17) and dynorphin-(1-8) had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum. The inhibition of contractions by dynorphin-(1-17) in three preparations was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors, indicating that dynorphin-(1-17) acted on kappa-receptors in three preparations. Additionally, the inhibitory potency of dynorphin-(1-17) relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in guinea-pig ileum was similar to that in either mouse vas deferens or rabbit ileum. This also suggested that dynorphin-(1-17) acted as a kappa-receptor agonist in three preparations. The effectiveness of naloxone and Mr 2266 to antagonize the agonist action of dynorphin-(1-8) indicated that dynorphin-(1-8) acted as a kappa-receptor agonist in either guinea-pig ileum or rabbit ileum whether or not peptidase inhibitors were existed while in mouse vas deferens it acted as a delta- or kappa-receptor agonist in the absence or presence of peptidase inhibitors, respectively. Thus, the choice of opioid receptor subtype in mouse vas deferens by dynorphin-(1-8) was likely to depend whether peptidases were inhibited or not. The inhibitory potency of dynorphin-(1-8) in the presence of peptidase inhibitors relative to that of ethylketocyclazocine in rabbit vas deferens, which had been shown to contain kappa-receptors exclusively, was similar to that in either mouse vas deferens or rabbit ileum, but was significantly different from that in guinea-pig ileum. This indicates that kappa-receptors in guinea-pig ileum are different from those in other preparations although the possibility of other causes such as incomplete inhibition of peptidase(s) can not be neglected.