Cyclic guanosine monophosphate is the mediator of platelet-activating factor inhibition on transport by the mouse kidney thick ascending limb

The Journal of Clinical Investigation
F NéantC Bailly

Abstract

Since we have previously shown a direct inhibitory effect of platelet-activating factor (PAF) on Cl reabsorption in the medullary thick ascending limb of Henle's loop (TAL), the aim of this study was to extend this effect to the whole TAL and to further investigate the signaling pathway involved. In microperfused cortical TALs, PAF significantly decreased Cl reabsorption by 50.3 +/- 6.5%. On the one hand, this effect was not modified in the presence of staurosporine and was not mimicked by phorbol ester; chelating cytosolic Ca by BAPTA/AM failed to suppress the inhibitory effect of PAF on Cl reabsorption; moreover, no significant increase in intracellular Ca concentration could be observed in the presence of PAF on isolated tubules. On the other hand, 8-bromo cyclic GMP mimicked the PAF effect on Cl reabsorption and prevented a further effect of this agent; the PAF effect was significantly reduced by H-8, a cyclic GMP-dependent protein kinase inhibitor; in medullary TALs, PAF significantly increased by twofold cyclic GMP content, an effect inhibited by the PAF antagonist BN 50730, whereas PAF did not significantly modify cAMP content in basal or stimulated conditions. Finally, inhibition of nitric oxide production by NAME or NM...Continue Reading

References

Oct 15, 1991·Biochemical and Biophysical Research Communications·R D YeC G Cochrane
May 31, 1991·Biochemical and Biophysical Research Communications·T TakanoK Kurokawa
Oct 1, 1984·Kidney International·M BrezisF H Epstein
Apr 1, 1994·Kidney International·J J MorrisseyS Klahr

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Citations

Dec 4, 1995·European Journal of Pharmacology·J GriderB Jackson
Sep 9, 2011·American Journal of Physiology. Renal Physiology·Gustavo R AresPablo A Ortiz
Aug 8, 2008·American Journal of Physiology. Renal Physiology·Gustavo R AresPablo A Ortiz
Mar 24, 2017·Antioxidants·Agustin Gonzalez-Vicente, Jeffrey L Garvin
Feb 28, 2019·American Journal of Physiology. Renal Physiology·Gustavo R Ares
Jan 31, 2020·Physiological Reviews·Jens Leipziger, Helle Praetorius
Jul 12, 2001·Journal of Hypertension·H Castrop, A Kurtz
Apr 6, 2002·American Journal of Physiology. Renal Physiology·Pablo A Ortiz, Jeffrey L Garvin
Jan 17, 2003·American Journal of Physiology. Renal Physiology·Rajash K HandaShelly E Handa

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