Demonstration of a specific dynorphin receptor in guinea pig ileum myenteric plexus

Abstract

Although the opioid peptide dynorphin contains the pentapeptide Leu-enkephalin as its amino-terminal sequence¹, the two opioid peptides differ in their potency and sensitivity to antagonism by the specific opiate antagonist naloxone. In the guinea pig myenteric plexus–longitudinal muscle assay, dynorphin_(1–13) is 700 times more potent and 13 times less sensitive to naloxone antagonism than Leu-enkephalin¹. We have identified the specific amino acids in the dynorphin_(6–13) sequence responsible for this higher potency². One explanation for the difference in naloxone sensitivities is that dynorphin and Leu-enkephalin act through different types of opiate receptors, as first suggested by Goldstein et al.¹. This hypothesis has been strongly supported by recent results³ showing that vasa deferentia of mice infused with both D-Ala²-D-Leu⁵-enkephalin (DADLE) and the opiate alkaloid sulfentanil become tolerant to the effects of Leu-enkephalin and sulfentanil, whereas sensitivity to dynorphina_(1–13) remains unchanged. Here we report that the guinea pig ileum myenteric plexus contains two physically distinct classes of opiate receptors: the μ receptor, with which leu-enkephalin (or normorphine) interacts, and a separate dynorphin receptor.