Abstract:
:A collection of analogues of atrial natriuretic peptide (ANP) were screened for their ability to inhibit ANP-induced cGMP stimulation. The antagonists revealed through this screen are structurally related; almost all are substituted at either aspartate-13 or phenylalanine-26. This tendency is consistent throughout several families of small ANP analogues, suggesting that these two amino acid residues are involved in the process of ANP/cGMP signal transduction. One compound, A74186, was studied in some detail. A74186 is a potent inhibitor of the activation of guanylate cyclase by ANP; it acts with a pA2 of 7.12 in rat vascular smooth muscle cells and shifts the ANP/cGMP dose-response curve by 3 orders of magnitude at a 10 microM concentration. It also inhibits cGMP release in vivo, and at an infusion rate of 10 micrograms/kg-min it completely abolishes ANP-induced natriuresis and diuresis. A74186 does not, however, antagonize the hypotensive or vasorelaxant effects of ANP; in fact it acts as an agonist in these assays. It thus appears that cGMP, although it may mediate the renal responses to ANP, is not responsible for the vascular and hemodynamic effects that result from the action of the hormone.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
von Geldern TW,Budzik GP,Dillon TP,Holleman WH,Holst MA,Kiso Y,Novosad EI,Opgenorth TJ,Rockway TW,Thomas AMsubject
Has Abstract,Author List Incompletepub_date
1990-12-01 00:00:00pages
771-8issue
6eissn
0026-895Xissn
1521-0111journal_volume
38pub_type
杂志文章abstract::Batrachotoxin (BTX), from South American frogs of the genus Phyllobates, irreversibly activates voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In this st...
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journal_title:Molecular pharmacology
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更新日期:1995-12-01 00:00:00
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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更新日期:1995-08-01 00:00:00
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journal_title:Molecular pharmacology
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更新日期:1996-04-01 00:00:00
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journal_title:Molecular pharmacology
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更新日期:1998-12-01 00:00:00
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journal_title:Molecular pharmacology
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更新日期:1987-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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更新日期:1995-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:1992-01-01 00:00:00
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更新日期:1986-12-01 00:00:00
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更新日期:1996-07-01 00:00:00
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journal_title:Molecular pharmacology
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doi:
更新日期:1994-07-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2000-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1998-06-01 00:00:00
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