Biologically active salmon calcitonin-like peptide is present in rat brain

Although high densities of calcitonin (CT) receptors and potent CT-induced actions occur within the rat central nervous system, the physiological ligand for central receptors remains unidentified. This study identifies a salmon CT (sCT)-like peptide in extracts of rat brain. Aliquots of 1 M HCl brain extracts were reconstituted in 0.01 M acetic acid and assayed for sCT-like immunoreactivity using a radioimmunoassay (RIA) based on a guinea pig anti-sCT antibody (detection limit 0.1 ng). The assay was less than 0.1% cross-reactive with human CT, porcine CT, rat calcitonin gene-related peptide (CGRP)-I and human CGRP-I. Extracts of diencephalon revealed sCT-like activity (30-120 ng/g wet weight), while extracts from cortex, cerebellum and medulla oblongata did not contain detectable activity. Reverse-phase HPLC analysis demonstrated co-elution with synthetic sCT. Further, the peak material was active in 4 CT bioassay systems; (1) stimulation of cAMP production in UMR 106-06 cells and (2) T47D cells, (3) inhibition of 125I-sCT binding in UMR 106-06 cells and (4) inhibition of 125I-sCT binding in sheep brain membranes. The bioactivity of material in these assays was similar to that estimated through the RIA. The results identify, for the first time, the presence of sCT-like material in the rat brain and constitutes the first demonstration of biologically active sCT-like material from brain extracts. Salmon CT-like peptide may represent the endogenous ligand for central CT receptors.