A naturally occurring opioid peptide from cow’s milk, beta-casomorphine-7, is a direct histamine releaser in man

β-Casomorphine-7, a naturally occurring product of cow’s milk with opiate-like activity, was studied for possible direct histamine liberation activities in humans. It was found to cause concentration-dependent in vitro histamine release from peripheral leukocytes of healthy adult volunteers. Intradermal injectionof β-casomorphine-7 induced a wheal and flare reaction in the skin similarto histamine or codeine. Oral pretreatment with the H₁ antagonist terfenadine significantly inhibited the skin responses to β-Casomorphine-7. The intradermal injection of an opiate receptor antagonist, naloxone, inhibited in vitro histamine release and skin reactions only in a 100-fold excess over β-Casomorphine-7. These findings suggest that β-Casomorphine-7 can be regarded as a noncytotoxic, direct histamine releaser in humans. The clinical relevance of these findings deserves further studies.