Structural requirements of ATP for activation of basal and atrial natriuretic factor-stimulated guanylate cyclase in rat lung membranes.
ATP has been reported to increase basal and atrial natriuretic factor (ANF)-stimulated guanylate cyclase activity. The structural features of ATP involved in the activation of guanylate cyclase were examined by employing a variety of ATP analogs with modification either at the phosphate chain or at the ribose moiety. Among the natural adenine nucleotides, ATP and ADP were able to increase both basal and ANF-stimulated guanylate cyclase activities in rat lung membranes. AMP had no effect. ATP was more effective than AMPPCP (the non-hydrolyzable analog of ATP), and ADP was more effective than ADP beta S and AMPCP (the hydrolysis-resistant analogs of ADP) to increase basal and ANF-stimulated guanylate cyclase activities. Removal of the oxygen atom from the ribose moiety of ATP or ADP significantly reduced their potency. Thus, the length of the phosphate chain and the hydroxyl groups at the ribose moiety are both determinants for nucleotide mediated guanylate cyclase activation.
Chang
C H
CH
Department of Medicine, University Hospital, Cleveland, Ohio.
Jiang
B
B
Douglas
J G
JG
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013873:Thionucleotides / Q000494:pharmacology
D013873:Thionucleotides; C472610:atrial natriuretic peptide, rat; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C030812:adenosine 5'-O-(2-thiodiphosphate); D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate