Calmodulin‐Sensitive and Calmodulin‐Insensitive Components of Adenylate Cyclase Activity in Rat Striatum Have Differential Responsiveness to Guanyl Nucleotides

Glenn J. Treisman, Stuart Bagley, Margaret E. Gnegy

Research output: Contribution to journalArticle

Abstract

Abstract: The interaction between the Ca2+‐binding protein, calmodulin, and guanyl nucleotides was investigated in a rat striatal paniculate fraction. We found that the ability of calmodulin to stimulate adenylate cyclase in the presence of guanyl nucleotides depends upon the type and concentration of the guanyl nucleotide. Adenylate cyclase activity measured in the presence of calmodulin and GTP reflected additivity at every concentration of these reactants. On the contrary, when the activating guanyl nucleotide was the nonhydrolyzable analog of GTP, guanosine‐5′‐(3,7‐imido)triphosphate (GppNHp), calmodulin could further activate adenylate cyclase only at concentrations less than 0.2 p.M GppNHp. Kinetic analysis of adenylate cyclase by GppNHp was compatible with a model of two components of adenylate cyclase activity, with over a 100‐fold difference in sensitivity for GppNHp. The component with the higher affinity for GppNHp was competitively stimulated by calmodulin. The additivity between calmodulin and GTP in the striatal particulate fraction suggests that they stimulate different components of cyclase activity. The cal‐modulin‐stimulatable component constituted 60% of the total activity. Our two‐component model does not delineate, at this point, whether there are two separate catalytic subunits or one catalytic subunit with two GTP‐binding proteins. The finding that GTP was unable to activate the calmodulin‐sensitive component suggests that this component has either a different mode of binding to a GTP‐binding protein or inherently higher GTPase activity than has the calmodulin‐insensitive component. The results suggest there are two components of adenylate cyclase activity that can be differentiated by their sensitivities to calmodulin and guanyl nucleotides.

Original languageEnglish (US)
Pages (from-to)1398-1406
Number of pages9
JournalJournal of Neurochemistry
Volume41
Issue number5
DOIs
StatePublished - May 1983

Keywords

  • Adenylate cyclase
  • Calcium
  • Calmodulin
  • GTP‐binding protein
  • Guanyl nucleotides
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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