Autoradiographic distribution of substance P receptors in rat central nervous system

Abstract

Among various neuropeptides present in the central nervous system (CNS), substance P, an undecapeptide¹, is of great interest as a putative pain neurotransmitter^2–4. Substance P is present within numerous intrinsic neural pathways throughout the CNS^5,6,36. Several groups have attempted to label substance P receptors on brain membranes by ligand binding techniques^7–12; only one study¹⁰ used native ³H-labelled substance P as the ligand and the precise anatomical distribution of substance P receptors has not yet been described. Here we report the autoradiographic localization of ³H-labelled substance P receptors in rat brain using the in vitro autoradiographic technique developed recently^13,14. ³H-substance P binds specifically to an apparently single class of sites on slide-mounted brain sections (K_d = 0.52 nM; B_max = 21.6 fmol per mg protein). The ligand selectivity pattern suggests that ³H-substance P binding sites are similar to those found in other assays^11,15. ³H-substance P receptors are highly concentrated in the external layers of the olfactory bulb, medial amygdala, dentate gyrus, superior colliculus, dorsal parabrachial nucleus and locus coeruleus, with moderate densities being found in the nucleus accumbens, striatum, periaqueductal grey and subiculum. The distribution of ³H-substance P receptors suggests that substance P is probably involved in the control of sensory processes such as pain, vision, audition and olfaction.