Key result
ANP and urodilatin significantly decreased intracellular pH in intercalated cells by 0.02 and 0.03 units, respectively, and decreased pH recovery after acidification.
In rat cortical collecting ducts, GC-A is located in the luminal membrane of intercalated cells where ANP acts to regulate intracellular pH via inhibition of the Na+/H+-exchanger.
Animal findings on ANP pH effects in rat intercalated cells should not change practice; leaves open translation to human renal physiology.
BACKGROUND: Natriuretic peptides regulate Na+ and H(2)O transport in the cortical collecting duct (CCD). We have shown that natriuretic peptides have no effect on ion conductances or water transport of principal cells (PC) even though a cGMP-regulated K+ channel is located in the basolateral membrane of these cells. METHODS: RT-PCR was used to screen for different guanylyl cyclases (GC) in CCD and to look for the expression of GC-1 and GC-A mRNA in CCD of male and female Wistar and Sprague-Dawley rats. Polyclonal antibodies were raised against the detected GC. BCECF was used to investigate the effects of ANP on intracellular pH in intercalated cells (IC). RESULTS: GC-A and GC-1 were detected. GC-A was immunolocalized in the luminal membrane of IC while GC-1 was mainly found in the luminal membrane of PC. GC-1 is expressed in Sprague-Dawley and Wistar rats except for male Sprague-Dawley rats, while GC-A is expressed in all strains. ANP (160 nM, n=11), urodilatin (140 nM, n=6), which had no effect in PC, significantly decreased pH(i) by 0.02+/-0.01 and 0.03 +/- 0.01 Units in IC, respectively. ANP as well as urodilatin and 8-Br-cGMP decreased the pH(i) recovery after acidification by 30 +/- 6% (n=12), 37 +/- 7% (n=8), and 19 +/- 3% (n=8), respectively. CONCLUSION: GC-A is located in the luminal membrane of IC of rat CCD and ANP acts through this receptor when regulating pH(i) via an inhibition of the Na+/H+-exchanger. PC do not possess GC-A. GC-1 seems to be the only GC in these cells of most rat strains tested and therefore, it could be responsible for the regulation of K+ channels in the basolateral membrane via cGMP-dependent protein kinase.
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Jochen R. Hirsch (2001) studied this question. ANP and urodilatin was evaluated on intracellular pH (pHi) in intercalated cells and pHi recovery after acidification. ANP and urodilatin significantly decreased intracellular pH in intercalated cells by 0.02 and 0.03 units, respectively, and decreased pH recovery after acidification.
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