Pre-clinical evaluation of dual targeting of the GPCRs CaSR and V2R as therapeutic strategy for autosomal dominant polycystic kidney disease.
Animals
Benzamides
/ pharmacology
Cyclic AMP
Drug Therapy, Combination
Female
Male
Mice
Mice, Inbred C57BL
Phenethylamines
/ pharmacology
Polycystic Kidney, Autosomal Dominant
/ drug therapy
Propylamines
/ pharmacology
Pyrroles
/ pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Calcium-Sensing
/ antagonists & inhibitors
Receptors, Vasopressin
/ chemistry
GPCRs
calcimimetics
calcium-sensing receptor
polycystic kidney disease
vaptans
vasopressin V2 receptor
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
30
07
2021
received:
13
05
2021
accepted:
09
08
2021
entrez:
6
9
2021
pubmed:
7
9
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations of PKD1 or PKD2 genes, is characterized by development and growth of cysts causing progressive kidney enlargement. Reduced resting cytosolic calcium and increased cAMP levels associated with the tonic action of vasopressin are two central biochemical defects in ADPKD. Here we show that co-targeting two GPCRs, the vasopressin V2 receptor (V2R) and the calcium sensing receptor, using the novel V2R antagonist lixivaptan in combination with the calcimimetic R-568, reduced cyst progression in two animal models of human PKD. Lixivaptan is expected to have a safer liver profile compared to tolvaptan, the only drug approved to delay PKD progression, based on computational model results and initial clinical evidence. PCK rat and Pkd1
Identifiants
pubmed: 34486176
doi: 10.1096/fj.202100774R
pmc: PMC9290345
doi:
Substances chimiques
Benzamides
0
N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
0
Phenethylamines
0
Propylamines
0
Pyrroles
0
Receptors, Calcium-Sensing
0
Receptors, Vasopressin
0
lixivaptan
8F5X4B082E
Cyclic AMP
E0399OZS9N
Types de publication
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21874Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
Références
Am J Nephrol. 2019;49(6):487-493
pubmed: 31117065
Kidney Int. 2011 Sep;80(6):612-9
pubmed: 21633408
Am J Physiol Renal Physiol. 2015 Jun 1;308(11):F1200-6
pubmed: 25656364
J Am Soc Nephrol. 2006 Jan;17(1):178-87
pubmed: 16319189
J Am Soc Nephrol. 2018 Oct;29(10):2458-2470
pubmed: 30228150
Kidney Int. 2003 Jun;63(6):1983-94
pubmed: 12753285
F1000Res. 2019 Feb 4;8:
pubmed: 30800291
Nat Rev Nephrol. 2016 Jul;12(7):414-25
pubmed: 27157444
J Am Soc Nephrol. 2005 Apr;16(4):846-51
pubmed: 15728778
J Am Soc Nephrol. 2020 Aug;31(8):1697-1710
pubmed: 32554753
N Engl J Med. 2012 Dec 20;367(25):2407-18
pubmed: 23121377
Nat Clin Pract Nephrol. 2006 Jan;2(1):40-55; quiz 55
pubmed: 16932388
J Am Soc Nephrol. 2015 Jan;26(1):39-47
pubmed: 24994926
Front Mol Biosci. 2018 Aug 24;5:77
pubmed: 30197885
Nephrol Dial Transplant. 2014 Sep;29 Suppl 4:iv15-25
pubmed: 25165182
Urolithiasis. 2019 Feb;47(1):23-33
pubmed: 30446806
J Biol Chem. 2004 Sep 24;279(39):40419-30
pubmed: 15263001
J Pharmacol Exp Ther. 2014 May;349(2):258-67
pubmed: 24570071
Kidney Int. 2001 Jan;59(1):126-36
pubmed: 11135065
Nat Med. 2003 Oct;9(10):1323-6
pubmed: 14502283
Pharm Res. 2020 Jan 6;37(2):24
pubmed: 31909447
Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2462-7
pubmed: 21262823
ScientificWorldJournal. 2007 Nov 12;7:1757-67
pubmed: 18040538
Eur J Pharmacol. 2014 Feb 5;724:67-76
pubmed: 24360935
J Nephrol. 2020 Apr;33(2):223-237
pubmed: 31853789
Exp Cell Res. 2017 Jan 1;350(1):50-61
pubmed: 27836810
FASEB J. 2018 Apr;32(4):2148-2159
pubmed: 29212817
N Engl J Med. 2008 Oct 2;359(14):1477-85
pubmed: 18832246
Nephrol Dial Transplant. 2018 Mar 1;33(3):477-489
pubmed: 28379536
Dev Genet. 1999;24(3-4):309-18
pubmed: 10322639
Nat Med. 2013 Apr;19(4):488-93
pubmed: 23524344
Exp Anim. 2000 Jan;49(1):51-5
pubmed: 10803363
Int J Mol Sci. 2019 Dec 26;21(1):
pubmed: 31888044
Cell Signal. 2020 Aug;72:109649
pubmed: 32335259
N Engl J Med. 2017 Nov 16;377(20):1930-1942
pubmed: 29105594
Core Evid. 2013;8:47-56
pubmed: 23874242
Vitam Horm. 2020;112:289-310
pubmed: 32061345
Nat Med. 2004 Apr;10(4):363-4
pubmed: 14991049
Sci Rep. 2018 Apr 9;8(1):5704
pubmed: 29632324
J Clin Invest. 2019 Jul 30;129(10):4506-4522
pubmed: 31361604
Kidney Int. 1992 Nov;42(5):1259-65
pubmed: 1453612
FASEB J. 2021 Oct;35(10):e21874
pubmed: 34486176
J Am Soc Nephrol. 2009 Jul;20(7):1527-32
pubmed: 19423689
J Am Soc Nephrol. 2006 Jun;17(6):1604-14
pubmed: 16641154
Nephrol Dial Transplant. 2009 Feb;24(2):526-34
pubmed: 18826972
Toxicol Sci. 2017 Jan;155(1):61-74
pubmed: 27655350
Am J Kidney Dis. 2016 May;67(5):792-810
pubmed: 26530876
Ann Nutr Metab. 2017;70 Suppl 1:43-50
pubmed: 28614813
Drug Saf. 2015 Nov;38(11):1103-13
pubmed: 26188764
J Clin Invest. 2012 Nov;122(11):4257-73
pubmed: 23064367