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Novel guanylyl cyclase inhibitor, ODQ reveals role of nitric oxide, but not of cyclic GMP in endothelin‐1 secretion
Author(s) -
Brunner Friedrich,
Stessel Heike,
Kukovetz Walter R.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01297-x
Subject(s) - soluble guanylyl cyclase , nitric oxide , guanylate cyclase , chemistry , secretion , cyclic gmp , endothelin 1 , endothelin receptor , medicine , endocrinology , biochemistry , pharmacology , biology , receptor , organic chemistry
The role of nitric oxide (NO) and guanosine 3′,5′‐cyclic monophosphate (cyclic GMP) in cellular regulation of endothelin‐1 (ET‐1) secretion was investigated in cultured porcine aortic endothelial cells. NO synthase was inhibited with ( l ‐NNA) and guanylyl cyclase with the novel selective inhibitor, ODQ (1 H ‐[1,2,4]oxadiazolo[4,3,‐a]quinoxalin‐1‐one) (3 μM). Basal and phorbol ester (PMA)‐stimulated ET‐1 secretion were unaffected by ODQ, but stimulated secretion was increased by l ‐NNA. In the presence of the NO donors, spermine/ NO, S ‐nitroso‐glutathione (GSNO), and nitroprusside (NP) ET‐1 secretion was reduced, but ODQ had no effect on this inhibition, although it effectively inhibited cyclic GMP production. NO release from donors, measured with a sensitive NO electrode, was greatest for spermine/NO, intermediate for GSNO, minimal for NP and paralleled inhibition of ET‐1 secretion. The data suggest that in cultured endothelial cells, curtailment of ET‐1 secretion is mediated by NO and independent of cyclic GMP.