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2015 ; 3
(3
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Effect of acute acid-base disturbances on the phosphorylation of phospholipase
C-?1 and Erk1/2 in the renal proximal tubule
#MMPMID25780091
Skelton LA
; Boron WF
Physiol Rep
2015[Mar]; 3
(3
): ä PMID25780091
show ga
The renal proximal tubule (PT) plays a major role in whole-body pH homeostasis by
secreting H(+) into the tubule lumen. Previous work demonstrated that PTs respond
to basolateral changes in [CO2] and [HCO3-] by appropriately altering H(+)
secretion-responses blocked by the ErbB inhibitor PD168393, or by eliminating
signaling through AT1 angiotensin receptors. In the present study, we analyze
phosphorylation of three downstream targets of both ErbBs and AT1: phospholipase
C-?1 (PLC-?1), extracellular-regulated kinase 1 (Erk1), and Erk2. We expose
rabbit PT suspensions for 5 and 20 min to our control (Ctrl) condition (5% CO2,
22 mmol/L HCO3-, pH 7.40) or one of several conditions that mimic acid-base
disturbances. We found that each disturbance produces characteristic
phosphorylation patterns in the three enzymes. For example, respiratory acidosis
(elevated [CO2], normal [HCO3-]) at 20 min decreases PLC-?1 phosphorylation at
tyrosine-783 (relative to Ctrl). Metabolic acidosis (normal [CO2], decreased
[HCO3-]) for 5 min increases Erk1 phosphorylation (p-Erk1) but not p-Erk2,
whereas metabolic alkalosis (normal [CO2], elevated [HCO3-]) for 5 min decreases
p-Erk1 and p-Erk2. In the presence of CO2/HCO3-, PD168393 blocks only two of
eight induced decreases in phosphorylation. In two cases in which disturbances
have no remarkable effects on phosphorylation, PD168393 unmasks decreases and in
two others, increases. These drug effects provide insight into the roles of
PD168393-sensitive kinases. Our results indicate that PLC-?1.pY783, p-Erk1, and
p-Erk2 in the PT change in characteristic ways in response to acute acid-base
disturbances, and thus presumably contribute to the transduction of acid-base
signals.