Linked Life Data

6300646

Source:http://linkedlifedata.com/resource/pubmed/id/6300646

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1983-5-5
pubmed:abstractText
Calcium ion is essential for normal stimulation of adrenal cortical adenylate cyclase by adrenocorticotropic hormone (ACTH). Both ACTH and Ca2+ act to promote the activation of adenylate cyclase by guanine nucleotides such as guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. To define further the mechanisms by which Ca2+ and ACTH interact with guanine nucleotides, we have correlated the binding of [3H]Gpp(NH)p to adrenal membranes and solubilized membrane proteins with activation of membrane-bound and solubilized adenylate cyclase. Ca2+ increases both the rate of reversible nucleotide binding and the rate of adenylate cyclase activation by nucleotide. This effect is accompanied by the appearance of binding sites having an 8- to 10-fold higher affinity for [3H]Gpp(NH)p. In contrast to Ca2+, ACTH increases the rate of enzyme activation but has no significant effect on nucleotide binding. In Ca2+-depleted membranes, measured nucleotide binding is low, and ACTH has no effect on enzyme activation. Once nucleotide is initially bound, both divalent cations and hormone can promote the transition of the enzyme to an activated state. Mg2+ is more effective than Ca2+ in promoting this transition, while Ca2+ is more effective than Mg2+ in promoting initial nucleotide binding. When membranes containing bound [3H]Gpp(NH)p are solubilized with Lubrol PX, adenylate cyclase activity elutes on Sepharose 4B with an apparent molecular weight of 160,000. The major fraction containing bound nucleotide elutes with an apparent molecular weight of 40,000-50,000. Nucleotide bound to this fraction is increased by pretreatment of the membranes with Ca2+ but is not affected by pretreatment with ACTH. Nucleotide bound to solubilized membrane components dissociates after treatment with EDTA. These findings suggest that Ca2+ promotes the initial binding of Gpp(NH)p to a biologically effective site that may involve a guanine nucleotide regulatory protein. ACTH activates adenylate cyclase by promoting a step subsequent to the binding of guanine nucleotide.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
369-77
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Activation of adrenal adenylate cyclase by guanine nucleotides. Promotion of nucleotide binding by calcium but not by adrenocorticotropic hormone.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.