POSTNATAL MATURATION OF THE KALLIKREIN-KININ SYSTEM IN THE RAT-KIDNEY- FROM ENZYME-ACTIVITY TO RECEPTOR GENE-EXPRESSION

During the course of aging, the balance between intrarenal hormones is disturbed. These age-related changes are well documented for the vaso constrictor renin-angiotensin system, but comparable information on th e renal kallikrein-kinin system is not yet available. The status of th e kallikrein-kinin system was assessed by (1) kallikrein activity, mea sured by RIA; (2) maximum binding site density (Bmax) and affinity (K- d) of nonapeptide bradykinin (BK)-2 receptor, estimated by binding ass ays; (3) expression of BK2-receptor mRNA, detected by reverse transcri ption-polymerase chain reaction (RT-PCR) using specific BK2-oligonucle otide primers. These parameters were determinated on renal glomeruli o f 3-, 5-, 8-, 12- and 38-wk-old normotensive rats. Kallikrein activity increased from 3.2 to 7.7 ng BK/min per mg protein. The density of BK 2 binding sites also rose from 12 to 40 femtomoles/mg protein with no difference in affinity. There was no change in specificity, which rema ined that expected of a BK2 receptor. The increase in the density of B K2 binding sites was associated with an augmented mRNA expression, whe reas beta-actin mRNA used as a control remained unchanged. The ratio o f BK2 mRNA to beta-actin mRNA indicated maximum steady expression afte r 8 wk of age. The data provide evidence that the renal kallikrein-kin in system develops postnatally.