This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jaken, S. Articles by Blumberg, P. M. Search for Related Content PubMed PubMed Citation Articles by Jaken, S. Articles by Blumberg, P. M.

Characterization of Phorbol Ester Receptors and Their Down-Modulation in GH₄C₁ Rat Pituitary Cells

Interdisciplinary Programs in Health [S. J.] and Laboratory of Toxicology [A. H. T.], Harvard School of Public Health, and Department of Pharmacology, Harvard Medical School [A. H. T., P. M. B.], Boston, Massachusetts 02115

Phorbol ester binding to intact GH₄C₁ cells, a continuous strain of rat pituitary cells, was measured using [³H]phorbol 12,13-dibutyrate. The binding was saturable; Scatchard analysis indicated one class of high-affinity binding sites (K_d, 11 nM) with 6.4 pmol [³H]phorbol 12,13-dibutyrate bound per mg cell protein at saturation. The relative binding affinities for other phorbol esters and analogs were similar to those demonstrated for binding to homogenates of chick embryo fibroblasts and mouse skin, as well as for tumor promotion in vivo. A close correlation was shown to exist between the binding affinities of these derivatives and their potencies for inducing biological responses in GH₄C₁ cells, such as decreases in binding of epidermal growth factor and thyrotropin-releasing hormone. A distinctive new finding is the down modulation of phorbol ester binding sites on GH₄C₁ cells by both homologous and heterologous ligands. Prolonged exposure to phorbol esters or thyrotropin-releasing hormone produced a loss of available [³H]-phorbol 12,13-dibutyrate binding sites with a maximal decrease to about 20% of control after 24 hr of treatment. Scatchard analysis indicated that the decrease in binding was due to a loss of receptors with no change in affinity. The biological significance of phorbol ester receptor down modulation is not yet known; however, it may represent a mechanism for attenuating cellular responsiveness to phorbol esters in their continued presence.

¹ Fellow of the Interdisciplinary Programs in Health, Harvard School of Public Health.

² Recipient of a research grant from the National Institute of Arthritis, Metabolism, and Digestive Diseases (AM 1101).

³ Recipient of a Research Career Development Award from NIH and a research grant from the National Cancer Institute (CA 22895). To whom requests for reprints should be addressed.

Received 11/24/80. Accepted 2/19/81.

This article has been cited by other articles:

				D. Chen, C. Gould, R. Garza, T. Gao, R. Y. Hampton, and A. C. Newton Amplitude Control of Protein Kinase C by RINCK, a Novel E3 Ubiquitin Ligase J. Biol. Chem., November 16, 2007; 282(46): 33776 - 33787. [Abstract] [Full Text] [PDF]

				K. Inagaki, R. Begley, F. Ikeno, and D. Mochly-Rosen Cardioprotection by {epsilon}-Protein Kinase C Activation From Ischemia: Continuous Delivery and Antiarrhythmic Effect of an {epsilon}-Protein Kinase C-Activating Peptide Circulation, January 4, 2005; 111(1): 44 - 50. [Abstract] [Full Text] [PDF]