Adenosine stimulates phosphate and glucose transport in opossum kidney epithelial cells

Abstract

We have examined the effects of adenosine on sodium-coupled phosphate and glucose transport in cultured opossum kidney (OK) cells, a continuous cell line that resembles proximal tubule. Adenosine analogues R-(-)-N6-phenylisopropyladenosine (PIA) and 2',5'-dideoxy-adenosine (DDA) were employed as adenosine A1 receptor and P site-selective agonists, respectively. Sodium-dependent phosphate uptake activity (Na-Pi symport) increased by approximately 25% above both basal and parathyroid hormone (PTH)-inhibited levels in cells treated with PIA (0.1, 1 microM) but not in cells treated with DDA (100 microM). Adenosine (PIA) also stimulated sodium-coupled 3-O-methylglucose transport by approximately 40%. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) content was inversely related to Na-Pi symport activity in cells treated with PIA and PTH. However, changes in Na-Pi symport activity did not consistently relate to changes in intracellular cAMP. Protein kinase C was activated 15 s after treatment of OK cells with 1 microM PIA. Preincubation of cells with 3 microM staurosporine attenuated the effect of 1 microM PIA on phosphate uptake. These data suggest that Na-Pi and Na-glucose symport activities are stimulated by adenosine acting at a receptor coupled to more than one intracellular signal. It is likely that both protein kinases A and C are involved in these actions of adenosine.

Requirement of Intact Adenosine A1Receptors for the Diuretic and Natriuretic Action of the Methylxanthines Theophylline and Caffeine

“…The observed diuresis and natriuresis in response to selective A 1 receptor blockade was caused by inhibition of proximal tubular reabsorption (Knight et al, 1993;van Buren et al, 1993;Wilcox et al, 1999). In accordance, in vitro studies in the proximal tubule showed that activation of A 1 receptor can stimulate transport of fluid, HCO 3 Ϫ as well as Na ϩ -glucose and Na ϩ -phosphate symport (Coulson et al, 1991;Takeda et al, 1993;Cai et al, 1994Cai et al, , 1995. The intracellular signaling pathways that contribute to these changes in tubular transport are still under investigation but may include reductions of intracellular cAMP levels (Kost et al, 2000), increases of intracellular Ca 2ϩ (Di Sole et al, 2003), and calcineurin homologous proArticle, publication date, and citation information can be found at http://jpet.aspetjournals.org.…”

Adenosine regulates a chloride channel via protein kinase C and a G protein in a rabbit cortical collecting duct cell line.

“…Elucidation of the renal tubular effects of adenosine is complicated by hormonally induced changes in hemodynamics and glomerular filtration rate that can mask direct effects of adenosine. Nevertheless, adenosine has been shown to antagonize vasopressin-stimulated water reabsorption in the cortical collecting duct (CCD)' (2) and inner medullary collecting duct (3), to stimulate Na+-phosphate and Na+-glucose transport in opossum kidney cells (4), and to inhibit the transepithelial voltage across isolated cortical thick ascending limbs of Henle's loop (5), suggesting a direct inhibitory action on sodium chloride reabsorption.…”

Endogenous adenosine contributes to renal sympathetic neurotransmission via postjunctional A1receptor-mediated coincident signaling

“…For example, in opossum kidney cells (proximal tubular phenotype), activation of A 1 adenosine receptors increases Na ϩ -phosphate and Na ϩ -glucose symport (7), and in rabbit proximal convoluted tubules, stimulation of A 1 receptors accelerates Na ϩ -3HCO 3 Ϫ symport in the basolateral membrane (56). It is now firmly established that activation of A 1 receptors augments proximal tubular sodium reabsorption (30,31,59,63).…”