Role of Src Family Kinase in Extracellular Renal Cyclic Guanosine 3′,5′-Monophosphate- and Pressure-Induced Natriuresis

Autor: Cláudia F. Santos, Nilberto R.F. Nascimento, Robert M. Carey, Nancy L. Howell, Thurl E. Harris, Brandon A. Kemp, John J Gildea
Rok vydání: 2011
Předmět:
Zdroj: Hypertension. 58:107-113
ISSN: 1524-4563
0194-911X
Popis: cGMP functions as an extracellular (paracrine) messenger acting at the renal proximal tubule and is an important modulator of pressure-natriuresis (P-N). The signaling pathway activated by cGMP in the tubule cell basolateral membrane remains unknown. We hypothesized that renal interstitial microinfusion of cGMP (50 nmol/kg per minute) or P-N would be accompanied by increased renal protein levels of phospho-Src (Tyr 416) and that the natriuresis would be decreased by Src inhibition. Renal interstitial cGMP-induced natriuresis was blocked by Src inhibitor PP2 (2.0±0.4 versus 0.5±0.01 μEq/g per minute; P P P + and lithium. Both extracellular cGMP and increased renal perfusion pressure increased renal phospho-Src protein levels and induced natriuresis in an Src-dependent manner, demonstrating that Src is an important downstream signaling molecule for extracellular cGMP-induced natriuresis.
Databáze: OpenAIRE