Neurotensin receptors in the human spinal cord: A quantitative autoradiographic study

Abstract

The anatomical localization of neurotensin receptors in the human spinal cord was examined in 12 cases aged 4–68 years using quantitative autoradiographic methods following the incubation of fresh, unfixed cryostat sections with 4 nM [ 3H]neurotensin. Characterization of the pharmacological specificity of the [ 3H]neurotensin binding sites in the human spinal cord from displacement studies with neurotensin 1–13 and various neurotensin fragments indicated that, whereas 1.0 μM neurotensin 1–13 and the car☐y-terminal fragment neurotensin 8–13 almost completely displaced [ 3H]neurotensin binding (4 nM), the ammo-terminal fragments neurotensin 1–8 and neurotensin 1–11 were weak inhibitors. This requirement for the car☐y-terminal fragment neurotensin 12–13 is consistent with [ 3H]neurotensin binding to specific neurotensin receptors in the human spinal cord. In all cases the autoradiograms demonstrated that neurotensin receptors were distributed in a similar fashion in the gray matter of the cervical, thoracic, lumbar, sacral and coccygeal regions of the human spinal cord. At all 21 spinal levels examined, the highest density of neurotensin receptors was localized in lamina II of the dorsal horn. Within lamina II the receptors were especially concentrated in the deeper inner segment (II j) where they formed a dense band lying immediately dorsal to lamina III. The density of receptors in this inner region of lamina II (23.5 fmol/mg) was almost double that in the outer segment of lamina II (12.2 fmol/mg), which showed the next highest density of receptors, and more than three times that in the adjacent lamina I (6.9 fmol/mg) and lamina III (7.1 fmol/mg). A moderate density of receptors was present in the intermediomedial (8.0 fmol/mg) and intermediolateral (8.0 fmol/mg) nuclei of lamina VII, and in lamina IX (4.4 fmol/mg). The density of labelling in the remaining laminae of the spinal cord was very low. These results indicate that neurotensin receptors are mainly localized in somatic and visceral sensory and motor regions of the human spinal cord and suggest that neurotensin may play a role in modulating sensory-motor functions in the human spinal cord.