Document Detail

The NHE3 inhibitor AVE1599 stimulates phrenic nerve activity in the rat.
MedLine Citation:
PMID:  18441385     Owner:  NLM     Status:  MEDLINE    
The effect of AVE1599, an inhibitor of the sodium/proton exchanger type 3 (NHE3), on phrenic nerve (PN) activity was investigated using the working heart brainstem preparation (WHBP). Hypercapnia (Delta pH: -0.1) applied for 10 min reversibly increased PN frequency (f) by 66.0 +/- 19.5% and decreased burst duration by 23.3 +/- 3% (mean +/- SE, n = 21). Similarly, AVE1599 (0.3 microM) increased f after 10 and 30 min by 75.1 +/- 13.2 and 176 +/- 36.2% (n = 10), respectively, and reduced duration of PN bursts by 24.9 +/- 10.8%. Hypercapnia-induced increases of f were attenuated by AVE1599. An elevated concentration of AVE1599 (0.9 microM) had no significant effect on PN. As AVE1599 accumulates in brain tissue and might interfere with the less affine NHE1, we furthermore tested the NHE1-inhibitor HOE642. In fact, HOE642 (0.9 microM) diminished f by 88.5 +/- 9.2 and 58.6 +/- 10.0% after 10 and 30 min (n = 6), respectively, but did not abolish hypercapnic responses. We conclude that AVE1599 augments central respiratory drive in the WHBP via NHE3 but not NHE1 inhibition.
M Wiemann; L Piechatzek; K Göpelt; H Kiwull-Schöne; P Kiwull; D Bingmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of physiology and pharmacology : an official journal of the Polish Physiological Society     Volume:  59     ISSN:  1899-1505     ISO Abbreviation:  J. Physiol. Pharmacol.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-04-28     Completed Date:  2008-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9114501     Medline TA:  J Physiol Pharmacol     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  27-36     Citation Subset:  IM    
Department of Physiology, University of Duisburg-Essen, Essen, Germany.
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MeSH Terms
Brain Stem / drug effects,  metabolism
Guanidines / pharmacology
Heart / drug effects,  innervation
Phrenic Nerve / drug effects*,  metabolism
Rats, Wistar
Respiration / drug effects*
Sodium-Hydrogen Antiporter / antagonists & inhibitors*,  drug effects,  metabolism
Sulfones / pharmacology
Time Factors
Reg. No./Substance:
0/Guanidines; 0/Slc9a1 protein, rat; 0/Sodium-Hydrogen Antiporter; 0/Sulfones; 0/cariporide; 0/sodium-hydrogen exchanger 3

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