TARGETS FOR SMR1-PENTAPEPTIDE SUGGEST A LINK BETWEEN THE CIRCULATING PEPTIDE AND MINERAL TRANSPORT

The submandibular rat 1 protein (SMR1) is selectively processed at pai rs of basic amino acid residues in a tissue-and sex-specific manner. W e have mapped peripheral targets for the final secretory maturation pr oduct of SMR1, the pentapeptide QHNPR, by examining in vivo the tissue distribution of the radiolabeled peptide using beta-radio imager whol e body autoradiography. The characteristics of tissue uptake allowed s pecific binding sites at physiological peptide concentrations to be id entified within the renal outer medulla, bone and dental tissue, gland ular gastric mucosa, and pancreatic lobules. Direct evidence that pent apeptide binding sites are localized in selective portions of the male rat nephron, within the S3, S2, and S1 segments of the proximal tubul es, was obtained. In bone tissue the pentapeptide exclusively accumula tes within the trabecular bone remodeling unit, and in dental tissue i t concentrates within the tubules of the dentinal rat incisor. In rela tion to male rat-specific behavioral characteristics, our data suggest that the circulating androgen-regulated SMR1-derived pentapeptide is primarily involved in the modulation of mineral balance between at lea st four systems: kidney, bone, tooth, and circulation.