title: Involvement of different receptor subtypes for the production of in vitro and in vivo effects in a series of synthetic enkephalin analogues.
abstract: Enkephalin analogues of tyrosyl group on the N-terminal and Phe-ol or phenylethylamine (PHA) group on the C-terminal which are connected with different chain length were tested for their activities in vitro and in vivo. The inhibitory effect of the synthetic peptides on the electrically evoked contractions of isolated longitudinal muscle strips of guinea pig ileum were weaker than that of morphine or Leu-enkephalin and tended to decrease by increasing the number of methylene group,-(CH2)n-, n = 1-5, between N- and C-terminal. Compounds with PHA group on the C-terminal, n = 4 and 5, showed the least activity. The effect of peptides with short chains of methylene groups, n = 1 or 2, and Phe-ol on the C-terminal were antagonized by naloxone but others were insensitive to naloxone. Differing from in vitro activity, compounds with PHA on the C-terminal with a chain of 4 methylene groups produced short lasting analgesia after i.c.v. injection as well as the compounds with Phe-ol on the C-terminal and 1 or 2 methylene groups. The analgesic effect of these compounds were completely antagonized by naloxone. At a high i.c.v. dose, all the synthetic peptides, except the one with PHA on the C-terminal with a chain of 4 methylene group, produced convulsions and/or ipsilateral rotation to the injection side. These behavioral effects were not antagonized by naloxone. Thus, minor alterations in the chemical structure of enkephalin analogues resulted in the changes of their receptor selectivity and potencies in vitro and in vivo.
mesh_terms: D000698:Analgesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000138:chemical synthesis / Q000494:pharmacology; D004745:Enkephalins / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D013997:Time Factors
chemical_list: D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D004743:Enkephalin, Leucine; D009020:Morphine