ULTRASTRUCTURAL-LOCALIZATION OF MU-OPIOID RECEPTORS IN THE SUPERFICIAL LAYERS OF THE RAT CERVICAL SPINAL-CORD - EXTRASYNAPTIC LOCALIZATION AND PROXIMITY TO LEU(5)-ENKEPHALIN

Many of the analgesic effects of opiate drugs and of endogenous opioid ligands, such as Leu(5)-enkephalin (LE) are thought to be mediated in part by mu-opioid receptors (MOR) in the dorsal horn of the spinal co rd. To establish the cellular sites for the spinally mediated analgesi c effects of MOR activation and the potential anatomical substrates fo r interactions with LE, we examined the ultrastructural localization o f MOR and LE immunoreactivities in the adult rat cervical spiral cord (C3-C5), Anti-MOR sera-recognizing the carboxyl terminal domain of MOR was localized using immunoperoxidase and immunogold-silver methods. C L-opioid receptor-like immunoreactivity (MOR-LI) was observed mainly i n the superficial layers of the dorsal horn. Electron microscopy of th is region revealed that small unmyelinated axons and axon terminals co nstituted 48% (91/189) and 15% (TL8/189), respectively, while dendrite s comprised 36% (68/189) of the total population of neuronal profiles containing the MOR. MOR-LI was localized mainly along extrasynaptic po rtions of the plasma membrane in both axons and dendrites. In sections dually labeled, for MOR and LE, 21% (14/68) of the dendrites containi ng MOR-LI closely apposed or received synaptic contact from axon termi nals :exhibiting LE reaction product. The results provide the first ul trastructural evidence that within the dorsal horn of the spinal cord, LE, as well as exogenous opiates may alter both axonal release of neu rotransmitters and postsynaptic responsiveness of target neurons to af f:trent input through activation of extrasynaptic MOR.