Linear alpha-human atrial natriuretic peptide analogs display receptor binding activity and inhibit alpha-hANP-induced cGMP accumulation.
We have synthesized a series of [Cys(R)7,23]alpha-hANP analogs, in which the two Cys residues were modified with various alkyl groups(R); i.e., R=Acm, Pe, Qe, Cam, Me, Ae, Bzl, Cm, Ocam and sulfo. The Acm-, Cam-, and Me-analogs exhibited binding activity as potent as alpha-hANP in rat vascular smooth muscle cells (VSMC). Binding activity of the analogs decreased progressively as the bulkiness of the R group increased. None of the analogs caused accumulation of cGMP in VSMC and vasorelaxant activity in rat aorta. Acm-, Cam- and Me-analogs substantially antagonized alpha-hANP-induced cGMP accumulation, but did not antagonize vasorelaxation induced by alpha-hANP in vitro.
Kitajima
Y
Y
Suntory Institute for Biomedical Research, Osaka, Japan.
Minamitake
Y
Y
Furuya
M
M
Takehisa
M
M
Katayama
T
T
Tanaka
S
S
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP