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Association of sequestered beta-adrenergic receptors with the plasma membrane: a novel mechanism for receptor down regulation.

Publication ,  Journal Article
Strader, CD; Sibley, DR; Lefkowitz, RJ
Published in: Life Sci
October 8, 1984

Chronic exposure of frog erythrocytes to beta-adrenergic agonists leads to desensitization of the responsiveness of adenylate cyclase to isoproterenol and is accompanied by "down-regulation", a decrease in the number of beta-adrenergic receptors on the cell surface. When frog erythrocyte plasma membranes are prepared by osmotic lysis of cells, the receptors lost from the cell surface during desensitization can be recovered in a "light membrane fraction", obtained by centrifuging the cell cytosol at 158,000 X g for 1 hr. These receptors are sequestered away from the plasma membrane fraction which contains the adenylate cyclase and the guanine nucleotide regulatory protein. If desensitized frog erythrocytes are disrupted by gentler freeze/thaw procedures, however, the sequestered beta-adrenergic receptors can be demonstrated to be physically associated with the plasma membrane. Typically, plasma membranes prepared in this fashion do not demonstrate a significant down regulation despite attenuation of isoproterenol-stimulated adenylate cyclase activity. Under these conditions, beta-adrenergic receptors from control and desensitized preparations co-migrate on sucrose density gradients in exactly the same place as the plasma membrane marker, adenylate cyclase. In contrast, when membranes from osmotically lysed desensitized cells are fractionated on sucrose gradients the down regulated receptors are sequestered in a light membrane fraction which barely enters the gradient and which is physically separated from adenylate cyclase activity. The data are consistent with a novel mechanism of receptor down-regulation which appears to involve the sequestration of the beta-adrenergic receptors away from the cell surface into a membrane compartment which remains physically associated with the plasma membrane.

Duke Scholars

Published In

Life Sci

DOI

ISSN

0024-3205

Publication Date

October 8, 1984

Volume

35

Issue

15

Start / End Page

1601 / 1610

Location

Netherlands

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Ranidae
  • Pharmacology & Pharmacy
  • Isoproterenol
  • Erythrocyte Membrane
  • Cell Membrane
  • Cell Compartmentation
  • Animals
  • Adenylyl Cyclases
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

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Strader, C. D., Sibley, D. R., & Lefkowitz, R. J. (1984). Association of sequestered beta-adrenergic receptors with the plasma membrane: a novel mechanism for receptor down regulation. Life Sci, 35(15), 1601–1610. https://doi.org/10.1016/0024-3205(84)90359-x
Strader, C. D., D. R. Sibley, and R. J. Lefkowitz. “Association of sequestered beta-adrenergic receptors with the plasma membrane: a novel mechanism for receptor down regulation.Life Sci 35, no. 15 (October 8, 1984): 1601–10. https://doi.org/10.1016/0024-3205(84)90359-x.
Strader, C. D., et al. “Association of sequestered beta-adrenergic receptors with the plasma membrane: a novel mechanism for receptor down regulation.Life Sci, vol. 35, no. 15, Oct. 1984, pp. 1601–10. Pubmed, doi:10.1016/0024-3205(84)90359-x.
Journal cover image

Published In

Life Sci

DOI

ISSN

0024-3205

Publication Date

October 8, 1984

Volume

35

Issue

15

Start / End Page

1601 / 1610

Location

Netherlands

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Ranidae
  • Pharmacology & Pharmacy
  • Isoproterenol
  • Erythrocyte Membrane
  • Cell Membrane
  • Cell Compartmentation
  • Animals
  • Adenylyl Cyclases
  • 3214 Pharmacology and pharmaceutical sciences