Bradykinin signaling counteracts cAMP-elicited aquaporin 2 translocation in renal cells.
Bradykinin (BK) is one of the most important peptides regulating vascular tone, water, and ionic balance in the body, playing a key role in controlling BP. It is interesting that patients with essential hypertension excrete less BK than normotensive individuals. For elucidating the mechanism by which BK regulates renal water transport that contributes to its antihypertensive effect, aquaporin 2 (AQP2)-transfected collecting duct CD8 cells, expressing the BK type II receptor (BK2R), were used as an experimental model. In CD8 cells, BK pretreatment impaired forskolin-induced AQP2 translocation to the apical plasma membrane. For clarifying the signal transduction cascade associated with this effect, whether BK induced an increase in cytosolic calcium, via the G protein Gq, known to be coupled to BK2R, first was investigated. Spectrofluorometry using fura-2-AM revealed that 100 nM BK elicited a significant increase in Ca(i), which was abolished by the receptor antagonist HOE-140. BK acts through BK2R coupled to both Gq and Galpha13, a known upstream effector of Rho protein. In CD8 cells, BK causes an increase in Rho activity, likely as a result of Galpha13 activation. This results in stabilization of the cortical F-actin network, thus impairing AQP2 trafficking. These effects counteract physiologic vasopressin stimulation, which instead has an opposite effect on actin network organization through Rho inactivation.
Tamma
Grazia
G
Dipartimento di Fisiologia Generale e Ambientale, Via Amendola 165/A, Bari 70126, Italy.
Carmosino
Monica
M
Svelto
Maria
M
Valenti
Giovanna
G
D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D007668:Kidney / Q000166:cytology* / Q000378:metabolism*; D021381:Protein Transport; D011817:Rabbits
D051399:Aquaporin 2; D005576:Colforsin; D000242:Cyclic AMP; D001920:Bradykinin; D002118:Calcium