Endogenous Morphine and Codeine As Possible Physiological Ligands of µ-Opiate Receptors

Abstract

Experiments carried out by indirect immunofluorescence and unlabelled antibody enzyme procedures revealed the presence of morphine-like immunoreactive material in the perikarya, fibers, and terminals of neurons in different, discrete areas of rat and human brain. The monoclonal and polyclonal anti-morphine antibodies used do not distinguish between morphine and codeine. Endogenous morphine seems to be stored in neurons as the 3-ethereal sulfate conjugate. This possibility is supported by the finding that, although active uptake of [3H]morphine has not been detected in brain synaptosomes, long-term i.c.v. injection of the tritiated opiate results in the accumulation of radioactivity inside the same neurons in which the endogenous alkaloids have been detected. Moreover, the sulfated compound showed a selective displacing effect toward [3H]DAMGO, although the affinity was lower than that of morphine HC1 and DAMGO. Finally, morphine-3-ethereal sulfate presented the same poor inhibitory action of morphine HC1 and DAMGO on rat striatal adenylate cyclase activity. Finally, striatal slices exposed to high K+ concentrations showed a rapid disappearance of the morphine-like immunoreactive material from neurons, indicating that endogenous alkaloids are released from neurons by depolarization.