Abstract：
:The dissociation constant (Kd) for the binding of epinephrine to beta-adrenergic receptors of the S49 cell is 2 microM, which is the ratio of the rate constants for dissociation (koff) and association (kon), Kd = koff/kon. Although the Kd is known by direct measurement, the individual rate constants kon and koff are unknown since they are both too large to be measured by conventional experimental methods. We present here an analysis in which a minimum value for these constants is calculated. The analysis uses a "transiently private receptor" model for coupling of receptors to G protein/adenylate cyclase that is based on the limits prescribed by the known empirical relationship between the beta-adrenergic receptor occupancy by epinephrine (characterized by Kd) and their coupling to adenylate cyclase (characterized by EC50 = 10 nM) as a function of epinephrine concentration. The model makes only the assumption (based on previous evidence) that a receptor cannot activate more than one cyclase during the course of one cycle of binding and unbinding of an epinephrine molecule. In such a model, and with such a large separation between the Kd and the EC50, the rate of G protein/adenylate cyclase activation by epinephrine-bound receptors can be related to the frequency of receptor binding at low concentrations of epinephrine, from which minimum values for the rate constant for association can be derived. This gives the estimates kon greater than 10(8)/M/min and koff greater than 280/min at 37 degrees. The on-rate constant is comparable to the on-rate constants that have been measured for other beta-adrenergic receptor ligands.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Stickle D,Barber Rdoi
10.1016/0006-2952(91)90290-lsubject
Has Abstractpub_date
1991-08-08 00:00:00pages
1069-77issue
5eissn
0006-2952issn
1873-2968pii
0006-2952(91)90290-Ljournal_volume
42pub_type
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journal_title：Biochemical pharmacology
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更新日期：1982-09-15 00:00:00
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pub_type： 杂志文章
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更新日期：1994-01-20 00:00:00
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更新日期：2000-06-15 00:00:00
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更新日期：1989-11-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1987-03-15 00:00:00
