Ontogeny of bradykinin B-2 receptors in the rat kidney: Implications for segmental nephron maturation

Kinins modulate renal function, yet their role in the developing kidney is largely unknown. To explore the developmental role of the kallikrein-kinin system, we examined the postnatal ontogeny and intrarenal localization of B-2 receptors in the rat. Northern blot analysis and RT-PCR documented the expression of B-2 receptor mRNA in the kidney and extrarenal tissues of fetal, neonatal and adult animals. The abundance of B-2 receptor mRNA is 10- to 30-fold higher in neonatal than adult tissues in the following order: kidney > heart > aorta > lung > brain. Receptor autoradiography revealed a gradual shift in the localization of bradykinin binding sites from the outer cortex in the newborn to the outer medulla in weanling and maturing rats. The almost complete displacement of [I-125]tyr(0)-bradykinin by HOE-140 indicates that the majority of kinin receptors in the developing kidney belong to the B-2 type. Immunolocalization studies using antipeptide antibodies directed against various portions of the receptor revealed that B-2 receptors are first expressed on the luminal aspect of the upper limb of S-shaped bodies and differentiating cortical collecting ducts. In marked contrast, the metanephric mesenchyme, pretubular aggregates and glomeruli display weak or no B-2 receptor immunoreactivity. Following completion of nephrogenesis, B-2 receptor expression shifts to both luminal and basolateral aspects of connecting tubules and collecting ducts. The results demonstrate that bradykinin B-2 receptor gene expression is activated in the developing kidney and cardiovascular system. The spatially restricted expression of B-2 receptors in the differentiating epithelium of the distal nephron, the site of kinin formation, supports the hypothesis that kinins are paracrine modulators of segmental nephron maturation.