Premium
ACTIONS OF ENDOTHELIN‐1 ON CULTURED RAT RENOMEDULLARY INTERSTITIAL CELLS ARE MODULATED BY NITRIC OXIDE
Author(s) -
Maric Christine,
Aldred G Peter,
Antoine Arianne M,
Eitle Eveline,
Dean Rachael G,
Williams David A,
Harris Peter J,
Alcorn Daine
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03060.x
Subject(s) - nitric oxide , intracellular , extracellular , endothelin receptor , endothelin 1 , receptor , nitric oxide synthase , medicine , endocrinology , second messenger system , atrial natriuretic peptide , inositol , chemistry , biology , microbiology and biotechnology , biochemistry
1. Cultured renomedullary interstitial cells (RMIC) isolated from 4‐week‐old Sprague‐Dawley rat kidneys possess ET A receptors, as identified by reverse transcription–polymerase chain reaction (RT‐PCR). 2. Treatment with endothelin (ET)‐1 (10 −6 mol/L) increases the intracellular inositol 1,4,5‐trisphosphate concentrations within 10 s and intracellular calcium concentrations after 7 s. 3. Endothelin‐1 (10 −7 and 10 −10 mol/L) induced increases in intracellular cAMP concentrations, but only in the presence of N ω ‐nitro‐ L ‐arginine, a nitric oxide synthase (NOS) inhibitor. Addition of ET‐1 (10 −10 mol/L) to the RMIC culture led to increases in intracellular cGMP concentrations through activation of NOS. 4. In the presence of ET‐1 (10 −7 and 10 −10 mol/L) and during NOS inhibition, RMIC responded with increased cell proliferation and extracellular matrix (ECM) synthesis. These responses were abolished by BQ‐123 (10 −6 mol/L), suggesting mediation via the ET A receptor subtype. The proliferative effect of ET‐1 was also abolished by atrial natriuretic peptide (10 −6 mol/L). 5. The present study provides evidence that binding of ET‐1 to ET A receptors on RMIC activates several intracellular second messenger systems that mediate cell proliferation and ECM synthesis. 6. These results also highlight an important interaction between ET‐1 and nitric oxide in the control of RMIC function.