Opioid receptor selectivity of dynorphin gene products.
In the guinea-pig ileum myenteric plexus-longitudinal muscle preparation, products from the dynorphin gene fell into three groups according to their potency. Dynorphin A was the most potent; dynorphin-32, dynorphin B, dynorphin B-29 and alpha-neo-endorphin were about equipotent and 10 to 20 times less potent than dynorphin A; dynorphin A-(1-8) and beta-neo-endorphin were about 200 times less potent than dynorphin A. Dynorphin A (a kappa agonist) was about 10 times less sensitive to antagonism by naloxone (as measured by naloxone Ke) than was normorphine (a mu agonist). Ke values for dynorphin-32, dynorphin B and alpha-neo-endorphin were the same as for dynorphin A, indicating that these peptides are also highly selective kappa agonists. Dynorphin A-(1-8), dynorphin B-29 and beta-neo-endorphin had Ke values intermediate between dynorphin A and normorphine, suggesting that they interact at both kappa and mu receptors. Addition of peptidase inhibitors to the bathing medium increased the potencies of dynorphin B, dynorphin B-29, alpha-neo-endorphin, dynorphin A-(1-8) and beta-neo-endorphin, but not of dynorphin A, dynorphin-32 or normorphine. The inhibitors did not change the naloxone Ke for dynorphin A or normorphine, or for dynorphin B-29, dynorphin A-(1-8) and beta-neo-endorphin, suggesting that the intermediate values were not caused by degradation to products with different receptor selectivities from the parent compounds. Ke for dynorphin-32, dynorphin B and alpha-neo-endorphin changed from being the same as dynorphin A in the absence of inhibitors to intermediate between dynorphin A and normorphine in the presence of inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004399:Dynorphins; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*
D004723:Endorphins; D010446:Peptide Fragments; D011498:Protein Precursors; D011957:Receptors, Opioid; D009270:Naloxone; D004743:Enkephalin, Leucine; D009271:Naltrexone; C017120:chlornaltrexamine; C025681:alpha-neoendorphin; D004399:Dynorphins; C036200:rimorphin