Linked Life Data

1646818

Source:http://linkedlifedata.com/resource/pubmed/id/1646818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1991-7-24
pubmed:abstractText
Cross-regulation from the stimulatory (Gs alpha)-mediated) to the inhibitory (Gi alpha-mediated) pathways controlling adenylylcyclase has been described (Hadcock, J. R., Ros, M., Watkins, D. C., and Malbon, C. C. (1990) J. Biol. Chem. 265, 14784-14790). The extent to which cross-regulation occurs from inhibitory to stimulatory pathways for adenylylcyclase was explored. Persistent activation of the inhibitory pathway of adenylylcyclase by the A1-adenosine receptor agonist (-)-N6 (R-phenylisopropyl) adenosine (PIA) in hamster smooth muscle DDT1 MF-2 cells enhanced the stimulatory pathway of adenylylcyclase and its activation by the beta 2-adrenergic receptor agonist isoproterenol. PIA treatment (48 h) of cells increased isoproterenol-stimulated adenylylcyclase by 2-fold. In addition, the ED50 for stimulation of adenylylcyclase by isoproterenol decreased 50-fold to approximately 1 nM. Persistent activation of cells with PIA increased beta 2-adrenergic receptor number in a time- and dose-dependent manner. The steady-state levels of beta 2-adrenergic receptors (radioligand binding and immunoblotting) and receptor mRNA levels increased by more than 70%, while the half-life of the receptor (24 h) was unaltered. Both A1-adenosine receptor binding and Gi alpha 2 levels declined by half in cells persistently activated with PIA. Although Gi alpha 2 mRNA levels and the relative rate of synthesis of Gi alpha 2 protein upon persistent activation of the inhibitory pathway were found to increase, a decrease in the half-life of Gi alpha 2 from approximately 75 h in naive cells to approximately 40 in cells provides the basis for the decline in Gi alpha 2 levels. The steady-state level of mRNA and half-life of Gs alpha protein were unaltered in persistently activated cells. Thus, activation of the inhibitory pathway of adenylylcyclase cross-regulates the stimulatory, hormone-sensitive adenylylcyclase system by: (i) up-regulating beta 2-adrenergic receptors and enhancing the activation of the stimulatory adenylylcyclase pathway and (ii) down-regulating elements of the inhibitory adenylylcyclase pathway (Gi alpha 2 and A1-adenosine receptor binding).
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11915-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1646818-Adenosine, pubmed-meshheading:1646818-Adenylate Cyclase, pubmed-meshheading:1646818-Animals, pubmed-meshheading:1646818-Blotting, Western, pubmed-meshheading:1646818-Cells, Cultured, pubmed-meshheading:1646818-Cricetinae, pubmed-meshheading:1646818-Cross Reactions, pubmed-meshheading:1646818-Down-Regulation, pubmed-meshheading:1646818-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:1646818-Enzyme Activation, pubmed-meshheading:1646818-GTP-Binding Proteins, pubmed-meshheading:1646818-Isoproterenol, pubmed-meshheading:1646818-Phenylisopropyladenosine, pubmed-meshheading:1646818-Precipitin Tests, pubmed-meshheading:1646818-RNA, Messenger, pubmed-meshheading:1646818-Radioligand Assay, pubmed-meshheading:1646818-Receptors, Adrenergic, beta, pubmed-meshheading:1646818-Up-Regulation
pubmed:year
1991
pubmed:articleTitle
Cross-regulation between G-protein-mediated pathways. Activation of the inhibitory pathway of adenylylcylclase increases the expression of beta 2-adrenergic receptors.
pubmed:affiliation
Department of Pharmacology, Diabetes and Metabolic Diseases Research Program, School of Medicine, State University of New York, Stony Brook 11794-8651.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't