Skip to main content
SpringerLink
Log in

B-HT 920 activates dopamine D2 receptors coupled to inhibition of adenylate cyclase activity

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

In homogenates of female rat anterior pituitary, the azepine derivative B-HT 920 inhibited the forskolin-stimulated adenylate cyclase activity with an EC50 value of 0.35 μM. In male rat anterior pituitary, B-HT 920 curtailed the stimulation of adenylate cyclase activity by vasoactive intestinal peptide with an EC50 of 0.20 μM. In synaptic plasma membranes of rat striatum, B-HT 920 significantly reduced basal adenylate cyclase activity with an EC50 of 0.68 μM. Both in pituitary and striatum, the B-HT 920 inhibition was counteracted by the dopamine (DA) D2 receptor antagonist 1-sulpiride, but not by the α2-adrenergic antagonist yohimbine. These results indicate that B-HT 920 is capable of activating DA D2 receptors negatively coupled to adenylate cyclase activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anden NE, Golembiowska-Nikitin K, Thornstrom U (1982) Selective stimulation of dopamine and noradrenaline autoreceptors by B-HT 920 and B-HT 933, respectively. Naunyn-Schmiedebergs Arch Pharmacol 321: 100–104

    Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254

    Google Scholar 

  • Cichini G, Placheta P, Singer EA (1987) B-HT 920 and B-HT 958: presynaptic effects on electrically evoked [3H] dopamine release from slices of rat nucleus accumbens. Naunyn-Schmiedebergs Arch Pharmacol 335: 28–31

    Google Scholar 

  • Cooper DMF, Bier-Laning CM, Halford MK, Ahlijanian MK, Zahniser NR (1986) Dopamine, acting through D2 receptors, inhibits rat striatal adenylate cyclase by a GTP-dependent process. Mol Pharmacol 29: 113–119

    Google Scholar 

  • Cote TE, Grewe CW, Kebabian JW (1981) Stimulation of a D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland decreases the responsiveness of the β-adrenoceptor: biochemical mechanism. Endocrinology 108: 420–426

    Google Scholar 

  • Drukarch B, Schepens E, Dolleman-Van der Weel J, De Boer P, Van Vliet BJ, Stoof JC (1990) Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum. Eur J Pharmacol 187: 257–269

    Google Scholar 

  • Enjalbert A, Bockaert J (1983) Pharmacological characterization of the D2 dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary. Mol Pharmacol 23: 576–584

    Google Scholar 

  • Enjalbert A, Sladeczek F, Guillon G, Bertrand P, Shu C, Epelbaum J, Garcia-Sainz A, Jard S, Lombard C, Kordon C, Bockaert J (1986) Angiotensin II and dopamine modulate both cAMP and inositol phosphate production in anterior pituitary cells. J Biol Chem 261: 4071–4075

    Google Scholar 

  • Freedman JE, Weight F (1988) Single K+ channels activated by D2 dopamine receptors in acutely dissociated neurons from rat corpus striatum. Proc Natl Acad Sci USA 85: 3618–3622

    Google Scholar 

  • Giannattasio G, De Ferrari ME, Spada A (1981) Dopamine-inhibited adenylate cyclase in female rat adenohypophysis. Life Sci 28: 1605–1612

    Google Scholar 

  • Giros B, Sokoloff P, Martres MP, Riou JF, Emorine LJ, Schwartz JC (1989) Alternative splicing directs the expression of two D2 dopamine receptors isoforms. Nature 342: 923–926

    Google Scholar 

  • Israel JM, Kirk C, Vincent JD (1987) Electrophysiological responses to dopamine of rat hypophysial cells in lactotrophs-enriched primary cultures. J Physiol 390: 1–22

    Google Scholar 

  • Jennewein HM, Bruckwick EA, Hanbauer I, Mierau J, Lovenberg W (1986) Evidence for a specific effect of B-HT 920, an azepine derivative, on tyrosine hydroxylase in a dopaminergic system of the rat. Eur J Pharmacol 123: 363–369

    Google Scholar 

  • Lacey MG, Mercuri NB, North RA (1987) Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J Physiol 392: 397–416

    Google Scholar 

  • Lafond J, Collu R (1986) Role of calcium and sodium ions in the inhibitory control of baseline and stimulated prolactin release. Endocrinology 119: 2012–2017

    Google Scholar 

  • Login IS, Judd AM, MacLeod RM (1988) Dopaminergic reduction of intracellular calcium: the role of calcium influx. Biochem Biophys Res Commun 151: 913–918

    Google Scholar 

  • Malgaroli A, Vallar L, Elahi FR, Pozzan T, Spada A, Meldolesi J (1987) Dopamine inhibits cytosolic Ca2+ increases in rat lactotroph cells. J Biol Chem 262: 13920–13927

    Google Scholar 

  • Memo M, Carboni E, Trabucchi M, Carruba MO, Spano PF (1985) Dopamine inhibition of neurotensin-induced increase in Ca2+ influx into rat pituitary cells. Brain Res 347: 253–257

    Google Scholar 

  • Monsma FJ Jr, McVittie LD, Gerfen CR, Mahan LC, Sibley DR (1989) Multiple D2 dopamine receptors produced by alternative RNA splicing. Nature 342: 926–929

    Google Scholar 

  • Olianas MC, Onali P, Neff NH, Costa E (1983) Adenylate cyclase activity of synaptic membranes from rat striatum. Inhibition by muscarinic receptors agonists. Mol Pharmacol 23: 393–398

    Google Scholar 

  • Onali P, Schwartz JP, Costa E (1981) Dopaminergic modulation of adenylate cyclase stimulation by vasoactive intestinal peptide in anterior pituitary. Proc Natl Acad Sci USA 78: 6531–6534

    Google Scholar 

  • Onali P, Olianas MC, Gessa GL (1985) Characterization of dopamine receptors mediating inhibition of adenylate cyclase activity in rat striatum. Mol Pharmacol 28: 138–145

    Google Scholar 

  • Salomon YD, Londos D, Rodbell M (1974) A highly sensitive adenylate cyclase assay. Anal Biochem 58: 541–548

    Google Scholar 

  • Schmidt CJ, Lobur A, Lovenberg W (1986) Inhibition of K+-stimulated [3H]dopamine and [14C] acetylcholine release by the putative dopamine autoreceptor agonist, B-HT 920. Naunyn-Schmiedebergs Arch Pharmacol 334: 377–382

    Google Scholar 

  • Schofield JG (1983) Use of a trapped fluorescent indicator to demonstrate effects of thyroliberin and dopamine on cytoplasmic calcium concentrations in bovine anterior pituitary cells. FEBS Lett 159: 79–82

    Google Scholar 

  • Seutin V, Scuvee-Moreau J, Giebers I, Massotte L, Dresse A (1990) Effect of B-HT 920 on monoaminergic neurons of the rat brain: an electrophysiological in vivo and in vitro study. Naunyn-Schmiedebergs Arch Pharmacol 242: 502–507

    Google Scholar 

  • Simmonds SH, Strange PG (1985) Inhibition of inositol phospholipid breakdown by D2 dopamine receptors in dissociated bovine anterior pituitary cells. Neurosci Lett 60: 267–272

    Google Scholar 

  • Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347: 146–151

    Google Scholar 

  • Woodruff GN, Freedman SB (1981) Binding of [3H]sulpiride to purified rat striatal synaptic membranes. Neuroscience 6: 407–410

    Google Scholar 

Download references

Author information

Author notes

  1. P. Onali

    Present address: Department of Neurosciences, University of Cagliari, Italy

Authors and Affiliations

  1. Department of Neurosciences, University of Cagliari, Italy

    M. C. Olianas

Authors
  1. P. Onali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. C. Olianas
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Onali, P., Olianas, M.C. B-HT 920 activates dopamine D2 receptors coupled to inhibition of adenylate cyclase activity. J. Neural Transmission 88, 95–104 (1992). https://doi.org/10.1007/BF01244815

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01244815

Keywords

Search

Navigation