SYNAPTIC RELATIONSHIP BETWEEN SUBSTANCE-P AND THE SUBSTANCE-P RECEPTOR - LIGHT AND ELECTRON-MICROSCOPIC CHARACTERIZATION OF THE MISMATCH BETWEEN NEUROPEPTIDES AND THEIR RECEPTORS

Light microscopic studies have demonstrated significant mismatches in the location of neuropeptides and their respective binding sites in th e central nervous system. In the present study we used an antiserum ra ised against a synthetic peptide corresponding to the carboxyl-termina l tail of the substance P (SP) receptor (SPR) to further explore the r elationship between a neuropeptide and its receptor. Light microscopy revealed an excellent correlation between the patterns of SPR immunore activity and of I-125-labeled SPR-binding sites in the central nervous system. The SPR appeared to be exclusively expressed by neurons; in f act, the SPR decorates the somatic and dendritic surface of neurons, p roducing Golgi-like images. Electron microscopic analysis in cortex, s triatum, and spinal cord revealed that approximately 70% of the surfac e membrane of immunoreactive neurons is SPR laden. Simultaneous electr on microscopic labeling of SP and SPR demonstrated significant mismatc h at the synaptic level. Although some SP terminals contacted SPR-immu noreactive membrane, no more than 15% of the SPR-laden membrane appose d synaptic terminals. These results suggest that in contrast to more ' 'classical'' central and peripheral nervous system synapses, wherein t he receptor immediately apposes the site of neurotransmitter storage a nd release, much of the surface of SPR-expressing neurons can be targe ted by SP that diffuses a considerable distance from its site of relea se.