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 vasoconstrictor renin-angiotensin system, but comparable information on the renal kallikrein-kinin system is not yet available. The status of the kallikrein-kinin system was assessed by (1) kallikrein activity, measured by RIA; (2) maximum binding site density (Bmax) and affinity (Kd) of nonapeptide bradykinin (BK)-2 receptor, estimated by binding assays; (3) expression of BK2-receptor receptor mRNA, detected by reverse transcription-polymerase chain reaction (RT-PCR) using specific BK2-oligonucleotide primers. These parameters were determinated on renal glomeruli of 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 BK2 binding sites also rose from 12 to 40 femtomoles/mg protein with no difference in affinity. There was no change in specificity, which remained that expected of a BK2 receptor. The increase in the density of BK2 binding sites was associated with an augmented mRNA expression, whereas beta-actin mRNA used as a control remained unchanged. The ratio of BK2 mRNA to beta-actin mRNA indicated maximum steady expression after 8 wk of age. The data provide evidence that the renal kallikrein-kinin system develops postnatally.
Bascands
J L
JL
INSERM U388, Institut Louis Bugnard, Toulouse, France.
Marin Castaño
M E
ME
Bompart
G
G
Pecher
C
C
Gaucher
M
M
Girolami
J P
JP
D000375:Aging / Q000502:physiology*; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D018002:Receptors, Bradykinin; D015232:Dinoprostone