Homologous and heterologous induction of the human bradykinin B1-receptor and B1-receptor localisation along the rat nephron.
The kinin B1-receptor which is absent or expressed at very low levels under physiological conditions is strongly induced under inflammatory conditions. It has been shown that B1-receptor induction during inflammation involves interleukin-1beta (IL-1beta) production and activation of nuclear factor-kappaB (NF-kappaB). Since bradykinin (BK), the B2-receptor agonist induces IL-1beta expression and activates NF-kappaB, we have analysed the effect of B2-receptor activation in cultured human lung fibroblasts cells on B1-receptor expression by a semiquantitative RT-PCR analysis. Treatment with BK resulted in a significant increase in the expression of B1-receptor mRNA which was abolished by a specific B2-receptor antagonist. This result suggests that B2-receptor activation can prime the expression of B1-receptors. Although the renal localisation of the B2-receptor has been thoroughly studied, nothing is known about the distribution of the B1-receptor in the kidney. Using a combination of microdissection and a semiquantitative RT-PCR/Southern blot analysis we showed the absence of B1-receptors under physiological conditions in 10 microdissected rat nephron segments. However, 18 h LPS-treatment induced significant expression of the B1-receptor in all, but one segment. These studies provide the first molecular basis for the observed changes in renal haemodynamics after B1-agonist infusion in animal kidney models.
Schanstra
J P
JP
INSERM U388, Institut Louis BUGNARD, CHU Rangueil, Toulouse, France.
Marin-Castaño
M E
ME
Alric
C
C
Pesquero
J B
JB
Claire
M
M
Girolami
J P
JP
Bascands
J L
JL
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009399:Nephrons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin