Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary.

Abstract

Binding sites for synthetic human 125-labeled calcitonin gene-related peptide (125I-CGRP) were demonstrated in membranes of the human CNS. Binding was high in the cerebellar cortex (1.35 .+-. 0.27 fmol/mg of tissue; mean .+-. SEM), spinal cord (1.06 .+-. 0.27 to 1.27 .+-. 0.23 fmol/mg) and nucleus dentatus (1.02 .+-. 0.15 fmol/mg), intermediate in the inferior colliculus (0.80 .+-. 0.14 fmol/mg), and substantia nigra (0.75 .+-. 0.14 fmol/mg), low in the neocortex, globus pallidus, nucleus caudatus, hippocampus, amygdala, superior colliculus, thalamus and hypothalamus (0.15-0.32 fmol/mg) and negligible in spinal and sympathetic ganglia and pituitary (< 0.04 fmol/mg). Autoradiography showed distinct 125I-CGRP binding over the molecular and Purkinje cell layers of the cerebellar cortex and over the substantia gelatinosa posterior of the spinal cord. The highest levels of CGRP-like components were recognized in the dorsal part of the spinal cord and the pituitary gland. In the ventral part of the spinal cord as well as in the pituitary and thyroid glands, CGRP values were higher when measured by radioreceptorassay as compared to RIA[radioimmunoassay], indicating that at least 2 CGRP-like components are present. The predominant CGRP-like peak of HPLC [high performance liquid chromatography] had the retention time of synthetic human CGRP. Immunohistochemistry revealed the presence of a dense plexus of CGRP immunoreactive nerve fibers in the dorsal horn of the spinal cord.