This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by CRONIN, M. J. Articles by WEINER, R. I. Search for Related Content PubMed PubMed Citation Articles by CRONIN, M. J. Articles by WEINER, R. I.

Absence of High Affinity Dopamine Receptors in GH₃Cells: A Prolactin-Secreting Clone Resistant to the Inhibitory Action of Dopamine^*

MICHAEL J. CRONIN, NACIA FAURE, JOSEPH A. MARTIAL and RICHARD I. WEINER

Departments of Obstetrics, Gynecology, and Reproductive Sciences and Medicine, University of California School of Medicine San Francisco, California 94143

Address all correspondence and requests for reprints to: Dr. Richard I. Weiner, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California School of Medicine, San Francisco,California 94143.

Abstract

Dopamine (DA) and DA agonists bind with high affinity to anterior pituitary receptors which mediate the inhibition of PRL release. Spiperone (SPIP), a DA antagonist, has also been successfully used to characterize pituitary DA receptors with a dissociation constant (K_d) of less than 1 nM. We studied the binding of SPIP to GH₃D₆ cells which secrete only PRL and GH. This clone was derived from a radiation-induced tumor of the rat anterior pituitary. Equilibrium binding of [³H]SPIP to living GH₃ cells showed no high affinity receptors, but a low affinity (K_d = 0.83 µM) and saturable (0.06 fmol/cell) population of sites was observed. In addition, saturable binding with a similar affinity (K_d = 0.57 µM) was noted in broken GH₃ cells. The interaction was completely reversible and temperature dependent. The concentrations of various ligands required to compete for half of the [³H]SPIP binding to whole cells were: chlorpromazine, 0.17 µM; haloperidol, 0.68 µM; pimozide, 0.77 µM; d-butaclamol, 1.16 µM; 1-butaclamol, 1.30 µM; SPIP, 1.49 µM; bromergocryptine, 4.98 µM; apomorphine, 13.9 µM; and DA, 100 µM. The absence of a high affinity site in GH₃ cells is consistent with the decreased effectiveness of various agonists and antagonists on PRL secretion. It is possible that the low affinity interactions observed in GH₃ cells are normally present in the anterior pituitary and brain and do not simply represent an alteration of receptor affinity. (Endocrinology 106: 718,1980)

Footnotes

^* This work was supported by NIH Grants HD-08924 and GM-25549.

Recipient of NIH Postdoctoral Fellowship NS-05506. Present address:Department of Physiology, Box 449, University of Virginia Medical School, Charlottesville, Virginia 22908.

Received May 21, 1979.

This article has been cited by other articles:

				G. Vlotides, O. Cooper, Y.-H. Chen, S.-G. Ren, Y. Greenman, and S. Melmed Heregulin Regulates Prolactinoma Gene Expression Cancer Res., May 15, 2009; 69(10): 4209 - 4216. [Abstract] [Full Text] [PDF]

				N. Ben-Jonathan Dopamine and Transforming Growth Factor-{beta}1: An Odd Couple in Growth Inhibition of the Lactotrophs Endocrinology, October 1, 2005; 146(10): 4177 - 4178. [Full Text] [PDF]

				S. E. Senogles The D2s Dopamine Receptor Stimulates Phospholipase D Activity: A Novel Signaling Pathway for Dopamine Mol. Pharmacol., August 1, 2000; 58(2): 455 - 462. [Abstract] [Full Text]