Advertisement

Evidence That the D-2 Dopamine Receptor in the Intermediate Lobe of the Rat Pituitary Gland Is Associated with an Inhibitory Guanyl Nucleotide Component

  • T. E. Cote
  • E. A. Frey
  • C. W. Grewe
  • J. W. Kebabian
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 18)

Summary

Stimulation of the D-2 dopamine receptor in the intermediate lobe (IL) of the rat pituitary gland diminishes both basal and isoproterenol-stimulated adenylate cyclase activity. Cholera toxin increases IL adenylate cyclase activity and reduces the ability of beta-adrenergic agonists to further enhance enzyme activity but does not alter the functioning of the D-2 dopamine receptor. Indeed, cholera toxin-treated IL tissue provides a useful experimental system to investigate the involvement of guanyl nucleotides in the functioning of the IL D-2 dopamine receptor. GTP is obligatory for dopaminergic agonists to inhibit adenylate cyclase activity of cholera toxin-treated IL tissue. Furthermore, 5′-guanylyl imidodiphosphate (Gpp[NH]p), a nonhydrolyzable analog of GTP, inhibits adenylate cyclase activity in the absence of a dopaminergic agonist. GTP reverses the Gpp(NH)p-induced inhibition of adenylate cyclase activity; apomorphine, a dopaminergic agonist, abolishes this effect of GTP. It is hypothesized that the D-2 dopamine receptor in the IL interacts with an inhibitory guanyl nucleotide component (Ni); stimulation of the D-2 dopamine receptor alters the properties of Ni so that Ni can interact with GTP and inhibit adenylate cyclase activity.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Kebabian, J. W., Calne, D. B.: Multiple receptors for dopamine. Nature (Lond.) 277, 93–96 (1979).CrossRefGoogle Scholar
  2. [2]
    Cote, T.E., Grewe, C. W., Kebabian, J. W: Stimulation of a D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland decreases the responsiveness of the ß-adrenoceptor; biochemical mechanism. Endocrinology 108, 420–426 (1981).CrossRefPubMedGoogle Scholar
  3. [3]
    Cote, T. E., Grewe, C. W., Tsuruta, K., Stoof, J. C, Eskay, R. L., Kebabian, J. W.: D-2 dopamine receptor-mediated inhibition of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland requires GTP. Endocrinology 110, 811–819 (1982).Google Scholar
  4. [4]
    Dube, D., Lissitzky, J. C., Leclerc, R., Pelletier, G.: Location of a-melanocyte-stimulating hormone in rat brain and pituitary. Endocrinology 102, 1283–1291 (1978).CrossRefPubMedGoogle Scholar
  5. [5]
    Rodbell, M.: The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature (Lond.) 284, 17–22 (1980).CrossRefGoogle Scholar
  6. [6]
    Bower, A., Hadley, M. E., Hruby, V.J.: Biogenic amines and control of melanophore stimulating hormone release. Science 184, 70–72 (1974).CrossRefPubMedGoogle Scholar
  7. [7]
    Cote, T, Munemura, M., Eskay, R. L., Kebabian, J. W.: Biochemical identification of the ß-adrenoceptor and evidence for the involvement of an adenosine 3’, 5’-monophosphate system in the ß-adrenergically induced release of a-melanocyte-stimulating hormone in the intermediate lobe of the rat pituitary gland. Endocrinology 107, 108–116 (1980).CrossRefPubMedGoogle Scholar
  8. [8]
    Meunier, H., Labrie, F.: Specificity of the ß2-adrenergic receptor stimulating cyclic AMP accumulation in the intermediate lobe of rat pituitary gland. Eur. J. Pharmacol. 81, 411–420 (1982).CrossRefPubMedGoogle Scholar
  9. [9]
    Cote, T. E., Grewe, C. W., Kebabian, J. W.: Guanyl nucleotides participate in the ß-adrenergic stimulation of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland. Endocrinology 110, 805–811 (1982).Google Scholar
  10. [10]
    Cassel, D., Selinger, Z.: Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc. Natl. Acad. Sci. 74, 3307–3311 (1977).CrossRefPubMedCentralPubMedGoogle Scholar
  11. [11]
    Kent, R. S., De Lean, A., Lefkowitz, R.J.: A quantitative analysis of ß-adrenergic receptor interactions: resolution of high and low affinity states of the receptor by computer modelling of ligand binding data. Mol. Pharmacol. 17, 14–23 (1979).Google Scholar
  12. [12]
    Munemura, M., Cote, T. E., Tsuruta, K., Eskay, R.L., Kebabian, J. W.: The dopamine receptor in the intermediate lobe of the rat pituitary gland: pharmacological characterization. Endocrinology 107, 1676–1683 (1980).Google Scholar
  13. [13]
    Stefanini, E., Devoto, P., Marchisio, A. M., Vernaleone, P., Collu, R.: [3H]- spiroperidol binding to a putative dopamine receptor in rat pituitary gland. Life Sci. 26, 583–587 (1980).CrossRefPubMedGoogle Scholar
  14. [14]
    Sibley, D. R., Creese, I.: Dopamine receptor binding in bovine intermediate lobe pituitary membranes. Endocrinology 107, 1405–1409 (1980).CrossRefPubMedGoogle Scholar
  15. [15]
    Frey, E.A., Cote, T. E., Grewe, C. W., Kebabian, J. W.: [3H]-spiroperidol identifies a D-2 dopamine receptor inhibiting adenylate cyclase activity in the intermediate lobe of the rat pituitary gland. Endocrinology 110, 1897–1904 (1982).CrossRefPubMedGoogle Scholar
  16. [16]
    Sibley, D. R., De Lean, A., Creese, I.: Anterior pituitary dopamine receptors. Demonstration of interconvertible high and low affinity states of the D-2 dopamine receptor. J. Biol. Chem. 257, 6351–6361 (1982).PubMedGoogle Scholar
  17. [17]
    De Lean, A., Kilpatrick, B. F., Caron, M. G.: Guanine nucleotides regulate both dopaminergic agonist and antagonist binding in porcine anterior pituitary. Endocrinology 110, 1064–1066 (1982).CrossRefPubMedGoogle Scholar
  18. [18]
    Giannattasio, G., De Ferrari, M.E., Spada, A.: Dopamine-inhibited adenylate cyclase in female rat adenohypophysis. Life Sci. 28, 1605–1612 (1981).CrossRefPubMedGoogle Scholar
  19. [19]
    Stoof, J. C., Kebabian, J. W: Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 294, 366–368 (1981).CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1983

Authors and Affiliations

  • T. E. Cote
    • 1
    • 2
  • E. A. Frey
    • 1
  • C. W. Grewe
    • 1
  • J. W. Kebabian
    • 1
  1. 1.Biochemical Neuropharmacology Section, Experimental Therapeutics BranchNINCDS, NIHBethesdaUSA
  2. 2.Biochemical Neuropharmacology Section, Experimental Therapeutics BranchNational Institute of HealthBethesdaUSA

Personalised recommendations