The release of beta-endorphin and the neuropeptide-receptor mismatch in the brain

Microprobes bearing immobilized antibodies to the carboxy-terminus of beta-endorphin were used to study the release of beta-endorphin in the urethane anaesthetized rat following electrical stimulation of the ipsilateral arcuate nucleus. The microprobes were inserted through the cerebral hemisphere, the superior colliculus and the midbrain periaqueductal grey. Since such microprobes detect extracellular molecules along their entire length they give information on the persistence and spread of compounds following release. Little immunoreactive-beta-endorphin was detected in the areas of brain sampled during electrical stimulation of arcuate nucleus but a remarkable spread throughout the midbrain and cerebral cortex occurred within 30 min of the cessation of stimulation. The results suggest that although beta-endorphin-containing fibres are absent in many parts of the brain, this neuropeptide can access receptors in these sites and it is not necessary for release to be directly adjacent to opiate receptors. As such it is important evidence supporting the hypothesis of volume transmission as a means of neuronal communication. The results also suggest that an important mechanism of the transport of beta-endorphin is the cerebrospinal fluid.