Stable expression of natriuretic peptide receptors: effects of HS-142-1, a non-peptide ANP antagonist.
We established clonal cell lines stably expressing each of two subtypes of membrane bound guanylate cyclases (GC-A and GC-B), which are known as natriuretic peptide receptors. Using these cell lines, we showed that GC-A is an ANP/BNP receptor, whereas GC-B is a specific receptor for CNP. Effects of HS-142-1, a novel non-peptide ANP antagonist, on GC-A and GC-B were examined by using these cells. In cells expressing either GC-A or GC-B, HS-142-1 inhibited cGMP production elicited by ANP or CNP with IC50 values of 1.8 micrograms/ml and 1.5 micrograms/ml, respectively, and also competitively blocked specific binding of the natriuretic peptides with IC50 values of 2.2 micrograms/ml and 3.3 micrograms/ml, respectively. These results indicate that HS-142-1 is a potent antagonist of CNP as well as ANP. We also showed that CNP suppressed the growth of cells expressing GC-B by 22% and that HS-142-1 blocked the antiproliferative action of CNP.
Ohyama
Y
Y
National Cardiovascular Center Research Institute, Osaka, Japan.
Miyamoto
K
K
Morishita
Y
Y
Matsuda
Y
Y
Saito
Y
Y
Minamino
N
N
Kangawa
K
K
Matsuo
H
H
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000378:metabolism*; D007700:Kinetics; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
C072551:HS 142-1; D011134:Polysaccharides; D009320:Atrial Natriuretic Factor; D004247:DNA; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP