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Effect of Acute Acid-Base Disturbances on ErbB1/2 Tyrosine Phosphorylation in Rabbit Renal Proximal Tubules.
MedLine Citation:
PMID:  24133121     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The renal proximal tubule (PT) is a major site for maintaining whole-body pH homeostasis and is responsible for reabsorbing ~80% of filtered bicarbonate (HCO3(-)), the major plasma buffer, into the blood. The PT adapts its rate of HCO3(-) reabsorption (JHCO3) in response to acute acid-base disturbances. Our laboratory previously showed that single isolated perfused PTs adapt JHCO3 in response to isolated changes in basolateral (i.e., blood-side) [CO2] and [HCO3(-)], but surprisingly not pH. The response to [CO2] is blocked by the ErbB-family tyrosine kinase inhibitor PD168393. In the present study, we expose enriched rabbit PT suspensions to five acute acid-base disturbances for 5 and 20 min, using a panel of phosphotyrosine (pY)-specific antibodies to determine the influence of each disturbance on pan-pY, ErbB1-specific-pY (four sites), and ErbB2-specific-pY (two sites). We find that each acid-base treatment generates a distinct temporal pY pattern. For example, the summated responses of the individual ErbB1/2-pY sites to each disturbance show that metabolic acidosis (normal [CO2], reduced [HCO3(-)]) produces a transient summated pY decrease (5 vs. 20 min), whereas metabolic alkalosis produces a transient increase. Respiratory acidosis (normal [HCO3(-)], elevated [CO2]) has little effect on summated pY at 5 min but produces an elevation at 20 min, whereas respiratory alkalosis produces a reduction at 20 min. Our data show that ErbB1 and ErbB2 in the PT respond to acute acid-base disturbances, consistent with the hypothesis that they are part of the signaling cascade.
Authors:
Lara Ann Skelton; Walter F Boron
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-10-16
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  -     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Case Western Reserve University.
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