ONTOGENY OF BRADYKININ B-2 RECEPTORS IN THE RAT-KIDNEY - IMPLICATIONSFOR SEGMENTAL NEPHRON MATURATION

Kinins modulate renal function, yet their role in the developing kidne y is largely unknown. To explore the developmental role of the kallikr ein-kinin system, we examined the postnatal ontogeny and intrarenal lo calization 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 e xtrarenal tissues of fetal, neonatal and adult animals. The abundance of B-2 receptor mRNA is 10- to 30-fold higher in neonatal than adult t issues 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 th e outer medulla in weanling and maturing rats. The almost complete dis placement of [I-125]tyr(0)-bradykinin by HOE-140 indicates that the ma jority of kinin receptors in the developing kidney belong to the B-2 t ype. Immunolocalization studies using antipeptide antibodies directed against various portions of the receptor revealed that B-2 receptors a re first expressed on the luminal aspect of the upper limb of S-shaped bodies and differentiating cortical collecting ducts. In marked contr ast, the metanephric mesenchyme, pretubular aggregates and glomeruli d isplay weak or no B-2 receptor immunoreactivity. Following completion of nephrogenesis, B-2 receptor expression shifts to both luminal and b asolateral aspects of connecting tubules and collecting ducts. The res ults demonstrate that bradykinin B-2 receptor gene expression is activ ated in the developing kidney and cardiovascular system. The spatially restricted expression of B-2 receptors in the differentiating epithel ium of the distal nephron, the site of kinin formation, supports the h ypothesis that kinins are paracrine modulators of segmental nephron ma turation.