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Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number.

Publication ,  Journal Article
Stadel, JM; De Lean, A; Mullikin-Kilpatrick, D; Sawyer, DD; Lefkowitz, RJ
Published in: J Cyclic Nucleotide Res
1981

Desensitization of turkey erythrocyte adenylate cyclase by exposure of these cells to the beta-adrenergic agonist isoproterenol leads to a decrease in subsequent adenylate cyclase stimulation by isoproterenol, F-, or Gpp(NH)p without any apparent loss or down regulation of receptors (B.B. Hoffman et al. J. Cyclic Nucl. Res. 5: 363-366, 1979). We now report that the desensitization is associated with a functional "uncoupling" of the beta-adrenergic receptor. This is evidenced by an impaired ability of receptors to form a high affinity, guanine nucleotide sensitive complex with agonist as assessed by computer analysis of radioligand binding data. The changes in adenylate cyclase responsiveness as well as the alterations in receptor affinity for agonists are reproduced by incubation of turkey erythrocytes with the cAMP analog 8-Bromo-adenosine 3':5'- cyclic monophosphate. These findings suggest that one possible mechanism for the development of desensitization in adenylate cyclase systems may be a cAMP mediated alteration of a component(s) of the beta-adrenergic receptor-adenylate cyclase complex which results in impaired receptor-cyclase coupling.

Duke Scholars

Published In

J Cyclic Nucleotide Res

ISSN

0095-1544

Publication Date

1981

Volume

7

Issue

1

Start / End Page

37 / 47

Location

United States

Related Subject Headings

  • Turkeys
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Isoproterenol
  • Erythrocytes
  • Drug Tolerance
  • Dihydroalprenolol
  • Cyclic AMP
  • Binding, Competitive
  • Animals
 

Citation

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Stadel, J. M., De Lean, A., Mullikin-Kilpatrick, D., Sawyer, D. D., & Lefkowitz, R. J. (1981). Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number. J Cyclic Nucleotide Res, 7(1), 37–47.
Stadel, J. M., A. De Lean, D. Mullikin-Kilpatrick, D. D. Sawyer, and R. J. Lefkowitz. “Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number.J Cyclic Nucleotide Res 7, no. 1 (1981): 37–47.
Stadel JM, De Lean A, Mullikin-Kilpatrick D, Sawyer DD, Lefkowitz RJ. Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number. J Cyclic Nucleotide Res. 1981;7(1):37–47.
Stadel JM, De Lean A, Mullikin-Kilpatrick D, Sawyer DD, Lefkowitz RJ. Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number. J Cyclic Nucleotide Res. 1981;7(1):37–47.

Published In

J Cyclic Nucleotide Res

ISSN

0095-1544

Publication Date

1981

Volume

7

Issue

1

Start / End Page

37 / 47

Location

United States

Related Subject Headings

  • Turkeys
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Isoproterenol
  • Erythrocytes
  • Drug Tolerance
  • Dihydroalprenolol
  • Cyclic AMP
  • Binding, Competitive
  • Animals