Premium
Endothelin‐1 affects AVP‐stimulated cAMP but not ANP‐induced cGMP productions in cultured rat IMCD cells
Author(s) -
ONO Shuichi,
KUSANO Eiji,
AMEMIYA Morimasa,
AKAI Yoichi,
TAKEDA Shigeyuki,
ANDO Yasuhiro,
HOMMA Sumiko,
ASANO Yasushi
Publication year - 1996
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.1996.tb00063.x
Subject(s) - medicine , peritoneal dialysis , dialysis , census , conversation , endothelin receptor , endocrinology , population , receptor , linguistics , philosophy , environmental health
Summary: The present study was undertaken to explore a potential interaction of endothelin‐1 (ET‐1) on vasopressin (AVP)‐dependent cyclic 3′,5′‐adenosine monophosphate (cAMP) and atrial natriuretic peptide (ANP)‐dependent cyclic 3′,5′‐guanosine monophosphate (cGMP) metabolisms in primary cultured rat inner medullary collecting duct (IMCD) cells. Endothelin‐1 did not affect ANP‐stimulated cGMP accumulation in the presence or absence of 3‐isobutyl‐1‐methylxanthine (IBMX). Levels of 10 −10 to 10 −7 mol/LET‐1 showed a dose‐dependent inhibition of the AVP‐dependent cAMP accumulation in the presence of IBMX and 10 −7 mol/LET‐1 inhibited the cAMP generation by 34 ± 5.3% ( n = 5, n = 20, P <0.01). Endothelin‐1 did not affect the cAMP generation either by 100 ng/mL cholera toxin or by 10 −4 mol/L forskolin. Endothelin‐1 failed to inhibit the cAMP generation in the presence of 100 ng/mL pertussis toxin (PTX). the inhibitory effect of ET‐1 was reversed by 10 −8 mol/L staurosporin (SSP), a protein kinase C (PKC) inhibitor. Furthermore, this inhibitory effect of ET‐1 was mimicked by 10 −8 mol/L phorbol 12‐myristate 13‐acetate (PMA), an activator of PKC. A dose of 5 × 10 −6 mol/L indomethacin did not affect this inhibitory effect of ET‐1. From these results, we suggest that the effect of ET‐1 on cyclic nucleotides metabolism seem to be selective. Endothelin‐1 did not affect the cGMP generation by ANP, whereas it inhibited cAMP production by AVP via PTX and SSP sensitive pathway in cultured rat IMCD cells.