Linked Life Data

6248606

Source:http://linkedlifedata.com/resource/pubmed/id/6248606

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1980-9-28
pubmed:abstractText
Using highly purified (greater than 95%) neutrophil (PMN) sonicates, we have studied the beta adrenergic (beta 1/beta 2) pattern of adenylate cyclase activation following agonist stimulation and have assessed the coupling characteristics of the beta adrenergic receptor to the adenylate cyclase enzyme. Adenylate cyclase was highly responsive to agonist activation, with peak isoproterenol (100 microM) stimulation resulting in the generation of 119 +/- 9.5 (mean +/- S.E.M.) pmol/mg/min cyclic AMP (224% above basal levels) compared to 171.7 +/- 8.6 following NaF (10 mM) stimulation. The agonist pattern of adenylate cyclase activation suggested the presence of beta-2 adrenergic receptors, since isoproterenol with a Kact of 0.7 microM was more potent than epinephrine (Kact = 8.5 microM) or norepinephrine (Kact = 90 microM). Butoxamine (beta-2 antagonist) was approximately 25 times more potent than practolol (beta-1 antagonist), with KDs of 0.75 microM and 17.5 microM, respectively. Receptor coupling efficiency was determined by measuring isoproterenol binding and adenylate cyclase activation with the same PMN sonicates and incubation conditions for each assay. The apparent KD for isoproterenol binding was 2.82 +/- 0.53 muM, the Kact was 0.47 +/- 0.05 muM, and the mean KD/Kact ratio was 6.5. Highly coupled receptor-enzyme systems have ratios greater than or equal to 1. Using sucrose gradient-purified PMN sonicates, we found that isoproterenol required the guanine nucleotides GTP or Gpp(NH)p to activate adenylate cyclase. The GTP effect on adenylate cyclase responsivenss to isoproterenol was associated with a 10-fold decrease in the isoproterenol binding affinity. These studies suggest that the human PMN has beta-2 adrenergic receptors which are highly coupled to the adenylate cyclase enzyme. We believe that this tissue offers a suitable model for the study of beta-2 adrenergic receptors and the mechanism of hormone-induced adenylate cyclase activation in man.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2143
pubmed:author
pubmed:issnType
Print
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1980
pubmed:articleTitle
Demonstration of beta-2 adrenergic receptors of high coupling efficiency in human neutrophil sonicates.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.