Humoral endorphin: can in vitro experiments explain in vivo results?

Humoral endorphin, an endogenous substance isolated from brain, blood and cerebrospinal fluid, reveals non-conventional interactions with both opiate agonist (morphine) and antagonist (naloxone) in the guinea pig ileum bioassay. The opioid activity of humoral endorphin is potentiated by pretreatment of the preparation with morphine and vice versa. Naloxone, a specific opiate antagonist, interacts with humoral endorphin in a distinct manner which distinguishes it from opiates: while low concentrations of naloxone antagonize the effect of humoral endorphin, high concentrations of the antagonist are less effective and even potentiate its opiate activity. These interactions between opiate agents can be explained assuming conformational transformation of the opiate receptor. The in vitro interactions shed new light on paradoxical and conflicting results of in vivo experiments and indicate the physiological function of humoral endorphin.