Morphological evidence of endomorphin as an agonist for the mu-opioid receptor in the rat spinal cord.

Endomorphin 2 is a newly discovered peptide that has high affinity and specificity for the mu-opioid receptor. One criterion for establishing that endomorphin serves as an endogenous agonist for the mu receptor is that it be anatomically distributed in close proximity to that receptor. We tested this idea with a preembedding double immunostaining technique to study synaptic relationships between them. The distributions of both endomorphin 2 and the mu-opioid receptor were similar in the dorsal horn of the cervical spinal cord at the light microscopic level. At the electron microscopic level, axon terminals with dense-cored vesicles containing endomorphin 2-like immunoreactivity were observed making mostly asymmetrical synapses on profiles immunostained for the mu-opioid receptor. The immunostaining for the mu-opioid receptor was found mostly in postsynaptic membranes in profiles having dendrite-like appearance. The results support the idea that endomorphin 2 is an endogenous ligand for the mu-opioid receptor. Furthermore, the results indicate that such a role is mediated at least in part through synaptic relationships.