Skip to main content
Journal cover image

Enhanced adenylate cyclase activity of turkey erythrocytes following treatment with beta-adrenergic receptor antagonists.

Publication ,  Journal Article
Peters, JR; Nambi, P; Sibley, DR; Lefkowitz, RJ
Published in: Eur J Pharmacol
December 15, 1984

The turkey erythrocyte contains a beta 1-adrenergic receptor-linked adenylate cyclase system. We have examined the effects of pretreatment with receptor antagonists on adenylate cyclase activity and the individual components in the pathway of enzyme activation in this system. Isoproterenol-stimulated adenylate cyclase activity is increased by 30% (P less than 0.01) over control in membranes derived from cells preincubated with the antagonist propranolol. The effect is stereospecific and dose-related with a EC50 of 100 nM for the (-) isomer. The time course of effect is rapid being complete by 90 min. Non-receptor mediated stimulation of adenylate cyclase activity by manganese ion, forskolin and NaF is similarly enhanced following propranolol pretreatment. Sensitization of adenylate cyclase activity also occurs following pretreatment with a number of antagonists but is not seen after preincubation with pindolol or practolol. Quantitation of beta-adrenergic receptor (R) density using [125I]cyanopindolol indicates no difference between membranes derived from control and antagonist pretreated cells. Coupling of R with the guanine nucleotide regulatory protein (N) as assessed by high affinity agonist binding is unchanged following pretreatment. The efficacy of 5'-guanylylimidodiphosphate Gpp(NH)p in producing a shift of agonist binding curves associated with destabilization of high affinity H-R-N complexes, is also the same (EC50 = 0.2 microM) in membranes from control and antagonist treated cells. The isoproterenol stimulated rate of release of [3H]GDP from membranes preloaded with [3H]GTP as an index of formation of an active form of the N protein is similarly unaffected by antagonist preincubation. We conclude that the mechanism of the observed sensitization of turkey erythrocyte adenylate cyclase by beta-adrenergic antagonists is receptor mediated and likely involves facilitation of N interaction with the catalytic subunit of the enzyme.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Eur J Pharmacol

DOI

ISSN

0014-2999

Publication Date

December 15, 1984

Volume

107

Issue

1

Start / End Page

43 / 52

Location

Netherlands

Related Subject Headings

  • Turkeys
  • Tritium
  • Receptors, Adrenergic, beta
  • Radioligand Assay
  • Radioisotopes
  • Propranolol
  • Pharmacology & Pharmacy
  • Isoproterenol
  • In Vitro Techniques
  • Guanosine Triphosphate
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Peters, J. R., Nambi, P., Sibley, D. R., & Lefkowitz, R. J. (1984). Enhanced adenylate cyclase activity of turkey erythrocytes following treatment with beta-adrenergic receptor antagonists. Eur J Pharmacol, 107(1), 43–52. https://doi.org/10.1016/0014-2999(84)90089-x
Peters, J. R., P. Nambi, D. R. Sibley, and R. J. Lefkowitz. “Enhanced adenylate cyclase activity of turkey erythrocytes following treatment with beta-adrenergic receptor antagonists.Eur J Pharmacol 107, no. 1 (December 15, 1984): 43–52. https://doi.org/10.1016/0014-2999(84)90089-x.
Peters JR, Nambi P, Sibley DR, Lefkowitz RJ. Enhanced adenylate cyclase activity of turkey erythrocytes following treatment with beta-adrenergic receptor antagonists. Eur J Pharmacol. 1984 Dec 15;107(1):43–52.
Peters, J. R., et al. “Enhanced adenylate cyclase activity of turkey erythrocytes following treatment with beta-adrenergic receptor antagonists.Eur J Pharmacol, vol. 107, no. 1, Dec. 1984, pp. 43–52. Pubmed, doi:10.1016/0014-2999(84)90089-x.
Peters JR, Nambi P, Sibley DR, Lefkowitz RJ. Enhanced adenylate cyclase activity of turkey erythrocytes following treatment with beta-adrenergic receptor antagonists. Eur J Pharmacol. 1984 Dec 15;107(1):43–52.
Journal cover image

Published In

Eur J Pharmacol

DOI

ISSN

0014-2999

Publication Date

December 15, 1984

Volume

107

Issue

1

Start / End Page

43 / 52

Location

Netherlands

Related Subject Headings

  • Turkeys
  • Tritium
  • Receptors, Adrenergic, beta
  • Radioligand Assay
  • Radioisotopes
  • Propranolol
  • Pharmacology & Pharmacy
  • Isoproterenol
  • In Vitro Techniques
  • Guanosine Triphosphate