May 2, 2015
R A Fenton et al, 2015, Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3, Am J Physiol Renal Physiol, article in press.
Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis; an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein coupled adenosine A1 receptor via the non-selective adenosine receptor antagonist caffeine changes Na+/H+ exchanger isoform 3 (NHE3) localization and phosphorylation resulting in diuresis and natriuresis. We generated tubulus-specific NHE3 knockout mice (Pax8-Cre), where NHE3 abundance in the S1, S2 and S3 segments of the proximal tubule was completely absent or severely reduced (>85%) in the thick ascending limb. Consumption of fluid and food, as well as glomerular filtration rate, were comparable in control or tubulus-specific NHE3 knockout mice under basal conditions, while urinary pH was significantly more alkaline without evidence for metabolic acidosis. Caffeine self-administration increased total fluid and food intake comparably between genotypes, without significant differences in consumption of caffeinated solution. Acute caffeine application via oral gavage elicited a diuresis and natriuresis that was comparable between control and tubulus-specific NHE3 knockout mice. The diuretic and natriuretic response was independent of changes in total NHE3 expression, phosphorylation of serine-552 and serine-605 or apical plasma membrane NHE3 localization. Although caffeine had no clear effect on localization of the basolateral Na+/bicarbonate cotransporter NBCe1, pretreatment with 4,4′-Diisothiocyanato-2,2′-stilbenedisulfonic acid (DIDS) inhibited caffeine-induced diuresis and natriuresis. In summary, NHE3 is not required for caffeine-induced diuresis and natriuresis.
Ja tak, jeg vil gerne modtage nyhedsbrev, når der er noget nyt om kaffe og helbred.