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. 1982 Sep;77(1):121–127. doi: 10.1111/j.1476-5381.1982.tb09277.x

Desensitization of prostacyclin receptors in a neuronal hybrid cell line.

I A Blair, P J Leigh, J MacDermot
PMCID: PMC2044635  PMID: 6289953

Abstract

1 Prostacyclin and its stable analogue, carbacyclin, bind competitively to a single population of receptors, and activate adenylate cyclase of the NCB-20 neuronal somatic cell hybrid (Kact = 40.1 nM and 96.1 nM respectively). 2 Culture of NCB-20 cells in the presence of 1 microM carbacyclin for 4 to 16 h results in a progressive decrease in the prostacyclin-dependent activation of adenylate cyclase in cell homogenates with an increase at 16 h of the Kact from 64.1 nM to 174.0 nM and decrease in the maximum adenylate cyclase activation from 41.2 to 15.1 pmol cyclic AMP min-1 mg-1 protein. 3 The prediction that the apparent decrease in affinity in the prostacyclin-dependent activation of adenylate cyclase was secondary to a reduction in receptor numbers was tested directly by measuring binding of [3H]-prostacyclin to membranes of cells exposed to carbacyclin for 16 h. This showed an actual decrease in affinity of the prostacyclin-receptor interaction, as well as a decrease in the total receptor numbers. Thus prolonged exposure of NCB-20 cells to carbacyclin caused reductions in both receptor numbers and affinity, reflected by measurements both of binding and adenylate cyclase activation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blair I. A., Hensby C. N., MacDermot J. Prostacyclin-dependent activation of adenylate cyclase in a neuronal somatic cell hybrid: prostanoid structure-activity relationships. Br J Pharmacol. 1980 Jul;69(3):519–525. doi: 10.1111/j.1476-5381.1980.tb07043.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blair I. A., MacDermot J. The binding of [3H]-prostacyclin to membranes of a neuronal somatic hybrid. Br J Pharmacol. 1981 Mar;72(3):435–441. doi: 10.1111/j.1476-5381.1981.tb10994.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cooper B., Schafer A. I., Puchalsky D., Handin R. I. Desensitization of prostaglandin-activated platelet adenylate cyclase. Prostaglandins. 1979 Apr;17(4):561–571. doi: 10.1016/0090-6980(79)90007-8. [DOI] [PubMed] [Google Scholar]
  4. Gorman R. R., Bunting S., Miller O. V. Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins. 1977 Mar;13(3):377–388. doi: 10.1016/0090-6980(77)90018-1. [DOI] [PubMed] [Google Scholar]
  5. Homburger V., Lucas M., Cantau B., Barabe J., Penit J., Bockaert J. Further evidence that desensitization of beta-adrenergic-sensitive adenylate cyclase proceeds in two steps. Modification of the coupling and loss of beta-adrenergic receptors. J Biol Chem. 1980 Nov 10;255(21):10436–10444. [PubMed] [Google Scholar]
  6. Kenimer J. G., Nirenberg M. Desensitization of adenylate cyclase to prostaglandin E1 or 2-chloroadenosine. Mol Pharmacol. 1981 Nov;20(3):585–591. [PubMed] [Google Scholar]
  7. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  8. Lefkowitz R. J., Mullikin D., Wood C. L., Gore T. B., Mukherjee C. Regulation of prostaglandin receptors by prostaglandins and guanine nucleotides in frog erythrocytes. J Biol Chem. 1977 Aug 10;252(15):5295–5303. [PubMed] [Google Scholar]
  9. MacDermot J., Barnes P. J. Activation of guinea pig pulmonary adenylate cyclase by prostacyclin. Eur J Pharmacol. 1980 Oct 31;67(4):419–425. doi: 10.1016/0014-2999(80)90183-1. [DOI] [PubMed] [Google Scholar]
  10. MacDermot J., Barnes P. J., Waddell K. A., Dollery C. T., Blair I. A. Prostacyclin binding to guinea pig pulmonary receptors. Eur J Pharmacol. 1981 Oct 22;75(2-3):127–130. doi: 10.1016/0014-2999(81)90071-6. [DOI] [PubMed] [Google Scholar]
  11. Minna J. D., Yavelow J., Coon H. G. Expression of phenotypes in hybrid somatic cells derived from the nervous system. Genetics. 1975 Jun;79 (Suppl):373–383. [PubMed] [Google Scholar]
  12. Minna J., Glazer D., Nirenberg M. Genetic dissection of neural properties using somatic cell hybrids. Nat New Biol. 1972 Feb 23;235(60):225–231. doi: 10.1038/newbio235225a0. [DOI] [PubMed] [Google Scholar]
  13. Newcombe D. S., Ciosek C. P., Jr, Ishikawa Y., Fahey J. V. Human synoviocytes: activation and desensitization by prostaglandins and 1-epinephrine. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3124–3128. doi: 10.1073/pnas.72.8.3124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pert C. B., Snyder S. H. Properties of opiate-receptor binding in rat brain. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2243–2247. doi: 10.1073/pnas.70.8.2243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature. 1980 Mar 6;284(5751):17–22. doi: 10.1038/284017a0. [DOI] [PubMed] [Google Scholar]
  16. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  17. Sharma S. K., Nirenberg M., Klee W. A. Morphine receptors as regulators of adenylate cyclase activity. Proc Natl Acad Sci U S A. 1975 Feb;72(2):590–594. doi: 10.1073/pnas.72.2.590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Siegl A. M., Smith J. B., Silver M. J., Nicolaou K. C., Ahern D. Selective binding site for [3H]prostacyclin on platelets. J Clin Invest. 1979 Feb;63(2):215–220. doi: 10.1172/JCI109292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sinzinger H., Silberbauer K., Horsch A. K., Gall A. Decreased sensitivity of human platelets to PGI2 during long-term intraarterial prostacyclin infusion in patients with peripheral vascular disease--a rebound phenomenon? Prostaglandins. 1981 Jan;21(1):49–51. doi: 10.1016/0090-6980(81)90195-7. [DOI] [PubMed] [Google Scholar]
  20. Su Y. F., Cubeddu L., Perkins J. P. Regulation of adenosine 3':5'-monophosphate content of human astrocytoma cells: desensitization to catecholamines and prostaglandins. J Cyclic Nucleotide Res. 1976 Jul-Aug;2(4):257–270. [PubMed] [Google Scholar]
  21. Tateson J. E., Moncada S., Vane J. R. Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins. 1977 Mar;13(3):389–397. doi: 10.1016/0090-6980(77)90019-3. [DOI] [PubMed] [Google Scholar]
  22. Whittle B. J., Moncada S., Whiting F., Vane J. R. Carbacyclin--a potent stable prostacyclin analogue for the inhibition of platelet aggregation. Prostaglandins. 1980 Apr;19(4):605–627. doi: 10.1016/s0090-6980(80)80010-4. [DOI] [PubMed] [Google Scholar]
  23. Whittle B. J., Steel G., Boughton-Smith N. K. Gastrointestinal actions of carbacyclin, a stable mimic of prostacyclin. J Pharm Pharmacol. 1980 Aug;32(8):603–604. doi: 10.1111/j.2042-7158.1980.tb13013.x. [DOI] [PubMed] [Google Scholar]

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