Botulinum Toxins Inhibit the Antidiuretic Hormone (ADH)-Stimulated Increase in Rabbit Cortical Collecting-Tubule Water Permeability |
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Authors: | Email author" target="_blank">R?QuigleyEmail author PY?Chu CL?Huang |
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Institution: | (1) Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75235-9063, USA;(2) Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9063, USA |
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Abstract: | The mammalian renal collecting duct increases its water permeability in response to antidiuretic hormone (ADH). ADH causes
cytoplasmic endosomes containing the water channel, aquaporin 2 (AQP2), to fuse with the apical membrane so that the water
permeability of the tubule increases many times above baseline. SNARE proteins are involved in the docking and fusion of vesicles
with the cell membrane in neuron synapses. Whether these proteins are involved in the fusion of vesicles to the cell membrane
in other tissues is not entirely clear. In the present study, we examined the role of SNARE proteins in the insertion of water
channels in the collecting-duct response to ADH by using botulinum toxins A, B and C. Toxins isolated from clostridium botulinum are specific proteases that cleave different SNARE proteins and inactivate them. Tubules were perfused in vitro with botulinum
toxin in the perfusate (50 nM for A and B and 15 nM for C). ADH (200 pM) was then added to the bath after baseline measurements
of osmotic water permeability (Pf) and the change in Pf was followed for one hour. Botulinum toxins significantly inhibited the maximum Pf by approximately 50%. Botulinum toxins A and C also decreased the rate of rise of Pf. Thus, SNARE proteins are involved in the insertion of the water channels in the collecting duct. |
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Keywords: | In vitro microperfusion Osmotic water permeability SNARE proteins |
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