H+ secretion is inhibited by clostridial toxins in an inner medullary collecting duct cell line

The American Journal of Physiology
Edward A AlexanderJohn H Schwartz

Abstract

Renal epithelial cell H+ secretion is an exocytic-endocytic phenomenon. In the inner medullary collecting duct (IMCD) cell line, which we have utilized as a model of renal epithelial cell acid secretion, we found previously that acidification increased exocytosis and alkalinization increased endocytosis. It is likely, therefore, that the rate of proton secretion is regulated by the membrane insertion and retrieval of proton pumps. There is abundant evidence from studies in the nerve terminal and the chromaffin cell that vesicle docking, membrane fusion, and discharge of vesicular contents (exocytosis) involve a series of interactions among so-called trafficking proteins. The clostridial toxins, botulinum and tetanus are proteases that specifically inactivate some of these proteins. In these experiments we demonstrated, by immunoblot and immunoprecipitation, the presence in this IMCD cell line of the specific protein targets of these toxins, synaptobrevin/vesicle-associated membrane proteins (VAMP), syntaxin, and synaptosomal-associated protein-25 (SNAP-25). Furthermore, we showed that these toxins markedly inhibit the capacity of these cells to realkalinize after an acid load. Thus these data provide new insight into the mechan...Continue Reading

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Citations

Feb 9, 2000·American Journal of Physiology. Renal Physiology·D Brown
May 12, 2000·American Journal of Physiology. Renal Physiology·S BretonD Brown
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Theodore R Muth, Michael J Caplan
Sep 8, 2005·American Journal of Physiology. Renal Physiology·Pablo A Ortiz
Sep 30, 2004·American Journal of Physiology. Renal Physiology·Tie-Jun SunChou-Long Huang
Nov 22, 2000·The Journal of Cell Biology·A ZahraouiT Galli
Mar 14, 2001·American Journal of Physiology. Cell Physiology·A BanerjeeJ H Schwartz
Sep 24, 2004·Physiological Reviews·Carsten A WagnerJohn P Geibel
Jul 9, 2004·American Journal of Physiology. Cell Physiology·Julie A NicolettaJohn H Schwartz

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