title: Activation of cardiac adenylate cyclase: horminal modification of the magnesium ion requirement.
abstract: Histamine and epinephrine stimulate the activity of guinea pig heart adenylate cyclase [ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1], in part, by decreasing the requirement for Mg2+ as an activator. This effect may represent an increase in affinity for Mg2+ and/or a decrease in sensitivity of the enzyme towards inhibition by free ATP. Both of these inotropic hormones also increase maximum velocity. Pretreatment of the membrane-bound enzyme with EDTA, to remove available divalent cations, almost eliminates persistent stimulation by guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Addition of Mg2+ to the preincubation medium restores the capacity of Gpp(NH)p to acutely activate the enzyme. These results indicate that Mg2+ interacts with the nucleotide (GTP) regulatory site. Persistent stimulation of the enzyme by either Gpp(NH)p or fluoride ion also involves a decrease in the requirement for Mg2+ and an increase in maximum velocity.
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D006150:Guanine Nucleotides; D006632:Histamine; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D008274:Magnesium; D004837:Epinephrine
references.citation: Biochemistry. 1964 Jan;3:18-26
references.pmid: 14114498
references.citation: J Biol Chem. 1975 Jun 10;250(11):4239-45
references.pmid: 1126949
references.citation: Proc Natl Acad Sci U S A. 1974 Aug;71(8):3087-90
references.pmid: 4607368
references.citation: J Biol Chem. 1974 May 10;249(9):2756-62
references.pmid: 4364028
references.citation: Anal Biochem. 1971 Sep;43(1):227-39
references.pmid: 4331761
references.citation: J Biol Chem. 1972 May 10;247(9):2949-58
references.pmid: 4337108
references.citation: J Biol Chem. 1971 Jul 10;246(13):4166-73
references.pmid: 5090039
references.citation: J Biol Chem. 1969 Jul 10;244(13):3468-76
references.pmid: 4307452
references.citation: J Biol Chem. 1970 Mar 10;245(5):976-83
references.pmid: 4313706
references.citation: Proc Natl Acad Sci U S A. 1976 Apr;73(4):1189-92
references.pmid: 4796
references.citation: J Biol Chem. 1975 Nov 10;250(21):8449-56
references.pmid: 1194261
references.citation: Adv Cyclic Nucleotide Res. 1975;5:3-29
references.pmid: 236641
references.citation: J Biol Chem. 1975 May 10;250(9):3459-65
references.pmid: 164469
references.citation: J Biol Chem. 1975 Jun 10;250(11):4253-60
references.pmid: 1126950
references.citation: J Biol Chem. 1975 Jun 10;250(11):4246-52
references.pmid: 236315
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713