Developmental expression and biological activity of gastrin-releasing peptide and its receptors in the kidney.

Abstract

Mammalian gastrin-releasing peptide (GRP) has a widespread distribution and multiple stimulating effects on metabolism, release of regulatory peptides, gastrointestinal and pancreatic secretions, and behavior. GRP is a potent mitogen for a number of tumor types, including colon and lung. Although GRP is known to stimulate the growth of renal tumors, little is known of its synthesis, distribution, and receptors in the developing and mature kidney. Both Northern blot analysis and RT-PCR revealed the presence of GRP mRNA in ovine kidney from midgestation through to adulthood. GRP mRNA was detected in rat kidney from embryonic day 19 to postnatal day 30 by RT-PCR. Sequence-specific radioimmunoassay demonstrated the presence of substantial amounts of fully processed amidated GRP in the ovine renal cortex and medulla. The mRNA for the major receptor subtype, GRP-R, was present in fetal and adult sheep and rat kidneys. The mRNA for the low-affinity GRP receptor, bombesin receptor subtype-3 (BRS-3), was only detected in the rat kidney. In the ovine kidney, immunohistochemistry localized GRP predominantly to the thick ascending limb of the loop of Henle. mRNAs for GRP, GRP-R, and BRS-3 were detected in the human embryonic kidney cell line HEK293, and radioimmunoassay of cell extracts and conditioned media revealed the presence of proGRP but not the amidated form. However, amidated GRP did stimulate the proliferation of these cells. These studies demonstrate that the developing and mature kidney may be previously unidentified sites of autocrine or paracrine action for GRP.