OPIOID RECEPTOR SELECTIVITY OF DYNORPHIN GENE-PRODUCTS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 228 (1), 88-93
Abstract
In the guinea pig ileum myenteric plexus-longitudinal muscle preparation, products from the dynorphin gene fell into 3 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 10-20 times less potent than dynorphin A; and 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 [the reciprocal of the affinity constant]) 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 were 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 interacted 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. Dynorphin A, dynorphin B and .alpha.-neo-endorphin all selectively protected the same receptors from inactivation by .beta.-chlornaltrexamine, suggesting that if there are .kappa. receptor subtypes in guinea pig ileum, they do not differentiate between these 3 gene products.