The histamine-releasing effect of dynorphin and other peptides possessing Arg-Pro sequences

The basic opioid peptide dynorphin was tested for histamine-releasing activity on peritoneal rat mast cells. Dynorphin was found to induce a dose-dependent histamine release from the mast cells. The threshold concentration was 2 X 10(-7) M and release was maximal (40% of total) at 2 X 10(-6) M of the peptide. The dynorphin-induced histamine release was a very rapid process completed within 10 seconds at 37 degrees C. The release was independent of extracellular calcium. Experiments with naloxone and a specific kappa-agonist (U-50,488H) gave results indicating that the dynorphin induced histamine release was probably not mediated through opioid kappa-receptors. A couple of other Arg-Pro containing peptides of different origin were also screened for histamine-releasing activity. Most of these peptides elicited a more or less pronounced histamine release, provided the peptide contained more than 5 amino acids, suggesting that the Arg-Pro sequence is of importance for the histamine-releasing effect of peptides such as dynorphin.