AT1 -receptor response to non-saturating Ang-II concentrations is amplified by calcium channel blockers

BMC Cardiovascular Disorders
Kristoffer BernhemLena Scott

Abstract

Blockers of angiotensin II type 1 receptor (AT1R) and the voltage gated calcium channel 1.2 (CaV1.2) are commonly used for treatment of hypertension. Yet there is little information about the effect of physiological concentrations of angiotensin II (AngII) on AT1R signaling and whether there is a reciprocal regulation of AT1R signaling by CaV1.2. To elucidate these questions, we have studied the Ca2+ signaling response to physiological and pharmacological AngII doses in HEK293a cells, vascular smooth muscle cells and cardiomyocytes using a Ca2+ sensitive dye as the principal sensor. Intra-cellular calcium recordings were performed in presence and absence of CaV1.2 blockers. Semi-quantitative imaging methods were used to assess the plasma membrane expression of AT1R and G-protein activation. Repeated exposure to pharmacological (100 nM) concentrations of AngII caused, as expected, a down-regulation of the Ca2+ response. In contrast, repeated exposure to physiological (1 nM) AngII concentration resulted in an enhancement of the Ca2+ response. The up-regulation of the Ca2+ response to repeated 1 nM AngII doses and the down-regulation of the Ca2+ response to repeated 100 nM Angll doses were not accompanied by a parallel change of t...Continue Reading

References

Mar 29, 1969·British Medical Journal·K J CattE Cran
Oct 19, 2001·Endocrinology·A Hus-CitharelC Llorens-Cortes
Oct 20, 2001·Cell Research·D F GuoT Inagami
Aug 23, 2002·Journal of the American Society of Nephrology : JASN·Akira NishiyamaL Gabriel Navar
Dec 13, 2005·International Journal of Cardiology·R M A van de WalA A Voors
Apr 18, 2006·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Jolanta WilimowskaEwa Florek
Feb 6, 2007·Biochemical Pharmacology·David J Triggle
Feb 23, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael J Beckstead, John T Williams
Nov 10, 2009·Journal of the American Board of Family Medicine : JABFM·Hean Teik Ong
Jan 5, 2010·Journal of the American Society of Hypertension : JASH·Minolfa C Prieto-CarrasqueroL Gabriel Navar
Aug 24, 2010·Molecular Interventions·James W Putney
Aug 28, 2010·Circulation Research·Gregory C AmbergStephanie A Glapa
Jan 13, 2011·JAMA : the Journal of the American Medical Association·Maria Eklind-CervenkaLars H Lund
Jan 21, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Simona PerraHitoshi Morikawa
Dec 24, 2011·Journal of the American Society of Nephrology : JASN·Dong LiAnita Aperia
Apr 30, 2014·The Journal of General Physiology·Jose MercadoLuis F Santana

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Citations

Oct 18, 2018·American Journal of Physiology. Renal Physiology·Michael FählingMichael Hultström

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Methods Mentioned

BETA
transfection
FRET
PCR

Software Mentioned

Matlab

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