In vivo and in vitro homologous desensitization of rat glomerular bradykinin B2 receptors.
We investigated the effects of bradykinin on glomerular bradykinin B2 receptor functions and parameters in vivo, after intrarenal infusion of bradykinin, and in vitro, after incubation of isolated rat glomeruli with bradykinin. Bradykinin transiently increased renal plasma flow whereas a second challenge was ineffective. Scatchard analysis demonstrated the presence of two populations of bradykinin binding sites whose densities were similarly decreased by about 40% after intrarenal bradykinin infusion. This decrease was not altered by an acid wash suggesting internalization of the radiolabelled ligand. The effect of bradykinin was prevented by a bradykinin B2 receptor antagonist. Pre-exposure of isolated rat glomeruli to bradykinin mimicked the in vivo results because there was a reduction in bradykinin-induced prostaglandin E2 and prostaglandin F2 alpha release. Rapid recovery was observed 15 min after washing out the bradykinin. Our results directly demonstrate a negative homologous down-regulation of B2 glomerular bradykinin receptor density under both in vivo and in vitro conditions, an effect which involves a rapid sequestration of the receptor.
Praddaude
F
F
Laboratory of Physiology Faculty of de Medicine, Toulouse, France.
Tack
I
I
Emond
C
C
Bascands
J L
JL
Girolami
J P
JP
Tran-Van
T
T
Regoli
D
D
Ader
J L
JL
D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007267:Injections; D007678:Kidney Glomerulus / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism*
D011453:Prostaglandins; D011506:Proteins; D018002:Receptors, Bradykinin; C026201:bradykinin, Tyr-; D001920:Bradykinin; D002118:Calcium