Linked Life Data

6116722

Source:http://linkedlifedata.com/resource/pubmed/id/6116722

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1981-12-21
pubmed:abstractText
beta-Adrenergic agonists form high affinity complexes with receptors, resulting in activation of the associated adenylate cyclase. To examine the formation of the high affinity state of the receptor, curves were constructed for the competition of the full beta-adrenergic agonist isoproterenol, partial agonists cobefrin and soterenol, and the antagonist propranolol for [3H]dihydroalprenolol binding to beta-adrenergic receptors on human neutrophil membranes. Curve modeling by computer yielded a two-state binding model for the agonists, with distinct dissociation constants for the high (KH) and low (KL) affinity states. The ratio of dissociation constants (KL/KH) was found to be well correlated (P less than 0.01) with the drug's intrinsic activity for stimulation of adenylate cyclase. Thus, the degree of coupling of receptor occupation with adenylate cyclase activation is correlated with the magnitude of KL/KH. Administration of cortisone to humans resulted in a substantial rise in the proportion of receptors in the high affinity state and in the KL/KH determined from isoproterenol competition curves, as well as a rise in adenylate cyclase activity. Furthermore, in vitro exposure of human neutrophils to hydrocortisone resulted in a similar rise in KL/KH determined from isoproterenol competition curves. Therefore, one mechanism by which cortisone modulates beta-adrenergic receptor function appears to be through facilitating the formation of the high affinity state of the receptor, resulting in greater coupling of receptor occupation with adenylate cyclase activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
703-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Agonist-promoted high affinity state of the beta-adrenergic receptor in human neutrophils: modulation by corticosteroids.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.