title: [Leu5]enkephalin containing peptides derived from a common precursor: evaluation of opioid activity in in vitro bioassays.
abstract: Opioid peptides containing the sequence of [Leu5]enkephalin were studied in two isolated organ preparations sensitive to opiates, the guinea pig ileum (GPI) and the mouse was deferens (MVD). All peptides tested were able to inhibit the electrically stimulated contraction in both tissues by interacting with specific receptors sensitive to the antagonist naloxone. Some of these peptides, mainly the shorter sequences, showed considerable potency differences in the two systems, suggesting that at least two different types of receptors are involved. Dynorphin-(1-17) displayed the highest agonistic potency in both preparations. In its case, there were no differences in IC50s nor in the shapes of the dose response curves in the two systems, suggesting a common receptor type; however, the reversal of its inhibitory effect following washout of the peptide was much more complete in the MVD than in GPI. Dynorphin B exhibited a higher potency in the GPI. Extension to dynorphin B-29 peptide did not induce changes in the agonistic activity in either system. An increase in one amino acid residue, dynorphin-(1-9) to -(1-10) or beta-neo-endorphin to alpha-neo-endorphin, resulted in a large potency increase in GPI and an opposite effect in MVD. While it has been reported that dynorphin interacts with the kappa opiate receptor in both mouse vas deferens and guinea pig ileum, our results suggest that the observable differences in the kinetics of the interaction in these systems could be due to the presence of different receptor types in these tissues.
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism / Q000502:physiology; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000378:metabolism* / Q000502:physiology
chemical_list: D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine