Novel genes and hormones in salivary glands: from the gene for the submandibular rat 1 protein (SMR1) precursor to receptor sites for SMR1 mature peptides

Submandibular rat 1 protein (SMR1) preprohormone and its maturation peptides constitute the novel characterized submandibular gland (SMG)-specific factors of the cervical sympathetic trunk (CST)-SMG (CST-SMG) axis. As is generally observed for major polypeptide hormones of the endocrine system, SMR1 peptides, including SMR1- imdecapeptide, -hexapeptide and -pentapeptide, are selectively matured from the precursor by cleavage at pairs of basic residues, and differentially accumulated and locally as well as systemically released under multifactorial neuroendocrine control. In turn, the final SMRl mature pentapeptide, at hormonal circulating concentrations, is selectively taken up by peripheral targets through specific binding sites. Localization of the target cells suggests that the SMRl-derived pentapeptide might be involved in modulating mineral ion balance in vivo. Furthermore, associated with male rat specific behavioral characteristics, one can propose that the androgen-regulated SMR1-pentapeptide is a SMG hormonal factor, which under stressful circumstances, is acutely secreted to counterregulate the mineral homeostatic responses to stress. The gene VCSA1, which encodes SMR1, belongs to a new multigene family, essentially expressed in the salivary glands of mammals. This family, whose several members also display putative sites of processing by convertases, has an unusual evolution characterized by multiple gene duplications and an accelerated divergence of coding sequences.Biomedical Reviews 1998; 9: 17-32