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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1976-12-23
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pubmed:abstractText |
The mechanism by which beta adrenergic agonist stimulate glycogenolysis in intact skeletal muscle was investigated in mice with the phosphorylase kinase deficiency mutation (I strain). Although extracts of I strain diaphragm muscle had only 3.7% of the phosphorylase kinase activity found in extracts of the control strain (C57BL), incubation of I strain hemidiaphragms in Krebs-Ringer bicarbonate buffer with either isoproterenol or epinephrine resulted in a stimulation of the rate of glycogenolysis. In C57BL diaphragms, the EC50 values for isoproterenol and epinephrine were 2 and 14 nM, respectively. With I strain diaphragms, dl-isoproterenol or l-epinephrine stimulated glycogenolysis as a linear function of the log of the drug concentration with no apparent plateau of response up to concentrations of 30 to 40 mugM. For each 10-fold increase in drug concentration, isoproterenol and epinephrine stimulated glycogenolysis in I strain muscles an additional 0.37 to 0.42 mg/g/hr, a slope in the concentration-response relationship of 0.17 and 0.37, respectively, of that measured in C57BL diaphragms at concentrations around the EC50. The highest glycogenolytic response measured in I strain hemidiaphragms (at 40 mugM isoproterenol) was 80% of the maximal catecholamine-stimulated glycogenolysis in C57BL diaphragms. Both 4 nM and 4 mugM isoproterenol, in a concentration-dependent manner, stimulated phosphorylase b to a conversion in I and C57BL diaphragms and increased cyclic adenosine 3':5'-monophosphate (cyclic AMP) concentrations. The glycogenolytic response to 10.1 nM dl-isoproterenol in both I and C57BL diaphragms was blocked by 34 nM l-propranolol but not by 34 nM d-propranolol. The response to 4 mugM isoproterenol was enhanced by the cyclic nucleotide phosphodiesterase inhibitors papaverine (27 mugM) or dl-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724, 3 mugM). From the results of these studies, we conclude: 1) Catecholamines stimulate glycogenolysis in skeletal muscle of I mice, as in C57BL mice, by interacting with the beta adrenergic receptor, thereby increasing tissue cyclic AMP concentrations and stimulating phosphorylase b to a conversion. 2) alternative hypotheses for the mechanism of the catecholamine-stimulated decrease in glycogen concentration in I skeletal muscle-inhibition of glycogen synthesis, hyposia and 5'-AMP stimulation of phosphorylase b activity-have been ruled out. 3) the activity of the mutant phosphorylase kinase, although it is only 3.7% of that in extracts of C57BL muscle, is sufficient to produce phosphorylase b to a conversion and thereby account for the glycogenolytic response of I strain muscle to catecholamines.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-(3-Butoxy-4-methoxybenzyl)-2-imida...,
http://linkedlifedata.com/resource/pubmed/chemical/Epinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Papaverine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphorylase Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphorylases,
http://linkedlifedata.com/resource/pubmed/chemical/Propranolol
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
198
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
526-38
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:978457-4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone,
pubmed-meshheading:978457-Animals,
pubmed-meshheading:978457-Epinephrine,
pubmed-meshheading:978457-Glycogen,
pubmed-meshheading:978457-Isoproterenol,
pubmed-meshheading:978457-Male,
pubmed-meshheading:978457-Mice,
pubmed-meshheading:978457-Mice, Inbred Strains,
pubmed-meshheading:978457-Muscles,
pubmed-meshheading:978457-Papaverine,
pubmed-meshheading:978457-Phosphorylase Kinase,
pubmed-meshheading:978457-Phosphorylases,
pubmed-meshheading:978457-Propranolol,
pubmed-meshheading:978457-Stimulation, Chemical
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pubmed:year |
1976
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pubmed:articleTitle |
Stimulation of glycogenolysis by beta adrenergic agonists in skeletal muscle of mice with the phosphorylase kinase deficiency mutation (I strain).
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pubmed:publicationType |
Journal Article
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