Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor.
During the search for ANP receptor ligands of microbial origin, we isolated a novel polysaccharide, HS-142-1, from culture broth of Aureobasidium sp. HS-142-1 inhibited [125I]-rANP binding to ANP receptor in rabbit kidney cortex membranes with an IC50 of 0.3 mu g/ml, but gave no effects on specific binding of [125I]-Endothelin nor [125I]-Angiotensin II to their respective receptors in bovine lung membranes. HS-142-1 competitively and selectively inhibited ANP binding to its guanylyl cyclase-containing receptor purified from solubilized bovine adrenocortical membranes and blocked cGMP production elicited by ANP. HS-142-1 is the first non-peptide antagonist selective for ANP functional receptor and will be a powerful tool to elucidate the physiological functions of ANP.
Morishita
Y
Y
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Sano
T
T
Ando
K
K
Saitoh
Y
Y
Kase
H
H
Yamada
K
K
Matsuda
Y
Y
D000302:Adrenal Cortex / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D016232:Endothelins / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D007700:Kinetics; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D017466:Receptors, Endothelin
D016232:Endothelins; D011134:Polysaccharides; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor