Uroguanylin inhibits H-ATPase activity and surface expression in renal distal tubules by a PKG-dependent pathway

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dc.contributor.authorLima V.S.
dc.contributor.authorCrajoinas R.O.
dc.contributor.authorCarraro-Lacroix L.R.
dc.contributor.authorGodinho A.N.
dc.contributor.authorDias J.L.G.
dc.contributor.authorDariolli R.
dc.contributor.authorGirardi A.C.C.
dc.contributor.authorFonteles M.C.
dc.contributor.authorMalnic G.
dc.contributor.authorLessa L.M.A.
dc.date.accessioned2024-03-13T01:00:09Z
dc.date.available2024-03-13T01:00:09Z
dc.date.issued2014
dc.description.abstract© 2014 the American Physiological Society. Cumulative evidence suggests that guanylin peptides play an important role on electrolyte homeostasis. We have previously reported that uroguanylin (UGN) inhibits bicarbonate reabsorption in a renal distal tubule. In the present study, we tested the hypothesis that the bicarbonaturic effect of UGN is at least in part attributable to inhibition of H+-ATPase-mediated hydrogen secretion in the distal nephron. By in vivo stationary microperfusion experiments, we were able to show that UGN inhibits H+-ATPase activity by a PKG-dependent pathway because KT5823 (PKG inhibitor) abolished the UGN effect on distal bicarbonate reabsorption and H89 (PKA inhibitor) was unable to prevent it. The in vivo results were confirmed by the in vitro experiments, where we used fluorescence microscopy to measure intracellular pH (pHi) recovery after an acid pulse with NH4Cl. By this technique, we observed that UGN and 8 bromoguanosine-cGMP (8Br-cGMP)inhibited H+-ATPase-dependent pHi recovery and that the UGN inhibitory effect was abolished in the presence of the PKG inhibitor. In addition, by using RT-PCR technique, we verified that Madin-Darby canine kidney (MDCK)-C11 cells express guanylate cyclase-C. Besides, UGN stimulated an increase of both cGMP content and PKG activity but was unable to increase the production of cellular cAMP content and PKA activity. Furthermore, we found that UGN reduced cell surface abundance of H+-ATPase B1 subunit in MDCK-C11 and that this effect was abolished by the PKG inhibitor. Taken together, our data suggest that UGN inhibits H+-ATPase activity and surface expression in renal distal cells by a cGMP/PKG-dependent pathway.
dc.description.firstpageC532
dc.description.issuenumber6
dc.description.lastpageC541
dc.description.volume307
dc.identifier.doi10.1152/ajpcell.00392.2013
dc.identifier.issn1522-1563
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/36364
dc.relation.ispartofAmerican Journal of Physiology - Cell Physiology
dc.rightsAcesso Restrito
dc.subject.otherlanguagecGMP
dc.subject.otherlanguageDistal tubule
dc.subject.otherlanguageH+-ATPase
dc.subject.otherlanguagePKG
dc.subject.otherlanguageRenal microperfusion
dc.subject.otherlanguageUroguanylin
dc.titleUroguanylin inhibits H-ATPase activity and surface expression in renal distal tubules by a PKG-dependent pathway
dc.typeArtigo
local.scopus.citations7
local.scopus.eid2-s2.0-84907148949
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84907148949&origin=inward
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