Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2009 Mar 24;25(2):43–53. doi: 10.1007/s12264-009-0107-0

Differential distributions and trafficking properties of dopamine D1 and D5 receptors in nerve cells

神经细胞中多巴胺D1和D5受体不同亚细胞分布和胞内转运的特性

You He 1, Lei-Ping Yu 1, Guo-Zhang Jin 1,✉
PMCID: PMC5552577  PMID: 19290022

Abstract

Objective

To explore the possible differential trafficking properties of the dopamine D1-like receptor subtypes, D1 receptor and D5 receptor.

Methods

To visualize distributions of dopamine D1-like receptor subtypes at subcellular level, the yellow and cyan variants of green fluorescent protein (GFP) were used to tag D1 and D5 receptors. After transfection with the tagged dopamine receptors, the neuroblastoma cells NG108-15 were treated with D1 agonist SKF38393 or acetylcholine (ACh). Then we observed the subcellular distributions of the tagged receptors under the confocal microscopy and tried to determine trafficking properties by comparing their distribution patterns before and after the drug treatment.

Results

In resting conditions, D1 receptors located in the plasma membrane of NG108-15 cells, while D5 receptors located in both plasma membrane and cytosol. With the pre-treatment of SKF38393, the subcellular distribution of D1 receptors was changed. The yellow particle-like fluorescence of tagged D1 receptors appeared in the cytosol, indicating that D1 receptors were internalized into cytosol from the cell surface. Same situation also occurred in ACh pre-treatment. In contrast, the subcellular distribution of D5 receptors was not changed after SKF38393 or ACh treatment, indicating that D5R was not translocated to cell surface. Interestingly, when D1 and D5 receptors were co-expressed in the same cell, both kept their distinct subcellular distribution patterns and the trafficking properties.

Conclusion

Our present study reveals that in NG108-15 nerve cells, dopamine D1 and D5 receptors exhibit differential subcellular distribution patterns, and only D1 receptor has a marked trafficking response to the drug stimulation. We further discuss the potential role of the differential trafficking properties of D1-like receptors in complex modulation of DA signaling.

Keywords: dopamine D1 receptor, dopamine D5 receptor, trafficking, internalization, green fluorescent protein, SKF38393, acetylcholine

References

  • [1].Kebabian J.W., Calne D.B. Multiple receptors for dopamine. Nature. 1979;277(5692):93–96. doi: 10.1038/277093a0. [DOI] [PubMed] [Google Scholar]
  • [2].O’Boyle K.M., Waddington J.L. Selective and stereospecific interactions of R-SK & F 38393 with [3H]piflutixol but not [3H] spiperone binding to striatal D1 and D2 dopamine receptors: comparisons with SCH 23390. Eur J Pharmacol. 1984;98(3–4):433–436. doi: 10.1016/0014-2999(84)90294-2. [DOI] [PubMed] [Google Scholar]
  • [3].Clark D., White F.J. D1 dopamine receptor—the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications. Synapse. 1987;1(4):347–388. doi: 10.1002/syn.890010408. [DOI] [PubMed] [Google Scholar]
  • [4].Monsma F.J., Mahan L.C., McVittie L.D., Gerfen C.R., Sibley D.R. Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. Proc Natl Acad Sci USA. 1990;87(17):6723–6727. doi: 10.1073/pnas.87.17.6723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].Sunahara R.K., Guan H.C., O’Dowd B.F., Seeman P., Laurier L.G., Ng G., et al. Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991;350(6319):614–619. doi: 10.1038/350614a0. [DOI] [PubMed] [Google Scholar]
  • [6].Tiberi M., Jarvie K.R., Silvia C., Falardeau P., Gingrich J.A., Godinot N., et al. Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor. Proc Natl Acad Sci USA. 1991;88(17):7491–7495. doi: 10.1073/pnas.88.17.7491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Weinshank R.L., Adham N., Macchi M., Olsen M.A., Branchek T.A., Hartig P.R. Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene. J Biol Chem. 1991;266(33):22427–22435. [PubMed] [Google Scholar]
  • [8].Dziewczapolski G., Menalled L.B., Garcia M.C., Mora M.A., Gershanik O.S., Rubinstein M. Opposite roles of D1 and D5 dopamine receptors in locomotion revealed by selective antisense oligonucleotides. Neuroreport. 1998;9(1):1–5. doi: 10.1097/00001756-199801050-00001. [DOI] [PubMed] [Google Scholar]
  • [9].Xu M., Hu X.T., Cooper D.C., Moratalla R., Graybiel A.M., White F.J., et al. Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice. Cell. 1994;79(6):945–955. doi: 10.1016/0092-8674(94)90026-4. [DOI] [PubMed] [Google Scholar]
  • [10].Centonze D., Grande C., Saulle E., Martin A.B., Gubellini P., Pavon N., et al. Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity. J Neurosci. 2003;23(24):8506–8512. doi: 10.1523/JNEUROSCI.23-24-08506.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Achour L., Labbé-Jullié C., Scott M.G.H., Marullo S. An escort for GPCRs: implications for regulation of receptor density at the cell surface. Trends Pharmacol Sci. 2008;29(10):528–535. doi: 10.1016/j.tips.2008.07.009. [DOI] [PubMed] [Google Scholar]
  • [12].Dumartin B., Caillé I., Gonon F., Bloch B. Internalization of D1 dopamine receptor in striatal neurons in vivo as evidence of activation by dopamine agonists. J Neurosci. 1998;18(5):1650–1661. doi: 10.1523/JNEUROSCI.18-05-01650.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Marie-Paule Muriel G.O.E.C.H. Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats. Movement Disorders. 2002;17(6):1174–1179. doi: 10.1002/mds.10256. [DOI] [PubMed] [Google Scholar]
  • [14].Jin G.Z., Zhu Z.T., Fu Y. (−)-Stepholidine: a potential novel antipsychotic drug with dual D1 receptor agonist and D2 receptor antagonist actions. Trends Pharmacol Sci. 2002;23(1):4–7. doi: 10.1016/S0165-6147(00)01929-5. [DOI] [PubMed] [Google Scholar]
  • [15].Higashida H., Yokoyama S., Hoshi N., Myojo Y., Kawamura T., Ito Y., et al. Phosphoinositides and synaptic function in NG108-15 neuroblastoma x glioma hybrid cells. Comp Biochem Physiol C. 1991;98(1):129–137. doi: 10.1016/0742-8413(91)90189-Z. [DOI] [PubMed] [Google Scholar]
  • [16].Luedtke R.R., Griffin S.A., Conroy S.S., Jin X., Pinto A., Sesack S.R. Immunoblot and immunohistochemical comparison of murine monoclonal antibodies specific for the rat D1a and D1b dopamine receptor subtypes. J Neuroimmunol. 1999;101(2):170–187. doi: 10.1016/S0165-5728(99)00142-3. [DOI] [PubMed] [Google Scholar]
  • [17].So C.H., Varghese G., Curley K.J., Kong M.M.C., Alijaniaram M., Ji X., et al. D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor. Mol Pharmacol. 2005;68(3):568–578. doi: 10.1124/mol.105.012229. [DOI] [PubMed] [Google Scholar]
  • [18].Gines S., Hillion J., Torvinen M., Le Crom S., Casadó V., Canela E.I., et al. Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. Proc Natl Acad Sci USA. 2000;97(15):8606–8611. doi: 10.1073/pnas.150241097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Morinville A., Cahill C.M., Esdaile M.J., Aibak H., Collier B., Kieffer B.L., et al. Regulation of delta-opioid receptor trafficking via muopioid receptor stimulation: evidence from mu-opioid receptor knock-out mice. J Neurosci. 2003;23(12):4888–4898. doi: 10.1523/JNEUROSCI.23-12-04888.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Jordan B.A., Trapaidze N., Gomes I., Nivarthi R., Devi L.A. Oligomerization of opioid receptors with β2-adrenergic receptors: A role in trafficking and mitogen-activated protein kinase activation. Proc Natl Acad Sci USA. 2001;98(1):343–348. doi: 10.1073/pnas.011384898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Bergson C., Levenson R., Goldman-Rakic P.S., Lidow M.S. Dopamine receptor-interacting proteins: the Ca2+ connection in dopamine signaling. Trends Pharmacol Sci. 2003;24(9):486–492. doi: 10.1016/S0165-6147(03)00232-3. [DOI] [PubMed] [Google Scholar]
  • [22].Bermak J.C., Li M., Bullock C., Zhou Q. Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein. Nat Cell Biol. 2001;3(5):492–498. doi: 10.1038/35074561. [DOI] [PubMed] [Google Scholar]
  • [23].Bermak J.C., Li M., Bullock C., Weingarten P., Zhou Q.Y. Interaction of gamma-COP with a transport motif in the D1 receptor C-terminus. Eur J Cell Biol. 2002;81(2):77–85. doi: 10.1078/0171-9335-00222. [DOI] [PubMed] [Google Scholar]
  • [24].Lee F.J., Xue S., Pei L., Vukusic B., Chéry N., Wang Y., et al. Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell. 2002;111(2):219–230. doi: 10.1016/S0092-8674(02)00962-5. [DOI] [PubMed] [Google Scholar]
  • [25].Liu F., Wan Q., Pristupa Z.B., Yu X.M., Wang Y.T., Niznik H.B. Direct protein-protein coupling enables cross-talk between dopamine D5 and -aminobutyric acid A receptors. Nature. 2000;403(6767):274–280. doi: 10.1038/35002014. [DOI] [PubMed] [Google Scholar]
  • [26].Heydorn A., Søndergaard B.P., Hadrup N., Holst B., Haft C.R., Schwartz T.W. Distinct in vitro interaction pattern of dopamine receptor subtypes with adaptor proteins involved in post-endocytotic receptor targeting. FEBS Letters. 2004;556(1–3):276–280. doi: 10.1016/S0014-5793(03)01431-5. [DOI] [PubMed] [Google Scholar]
  • [27].Iwasiow R.M., Nantel M.F., Tiberi M. Delineation of the Structural Basis for the Activation Properties of the Dopamine D1 Receptor Subtypes. J Biol Chem. 1999;274(45):31882–318890. doi: 10.1074/jbc.274.45.31882. [DOI] [PubMed] [Google Scholar]
  • [28].Demchyshyn L.L., McConkey F., Niznik H.B. Dopamine D5 receptor agonist high affinity and constitutive activity profile conferred by carboxyl-terminal tail sequence. J Biol Chem. 2000;275(31):23446–23455. doi: 10.1074/jbc.M000157200. [DOI] [PubMed] [Google Scholar]
  • [29].Seamans J.K., Yang C.R. The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol. 2004;74(1):1–58. doi: 10.1016/j.pneurobio.2004.05.006. [DOI] [PubMed] [Google Scholar]
  • [30].Williams G.V., Goldman-Rakic P.S. Modulation of memory fields by dopamine Dl receptors in prefrontal cortex. Nature. 1995;376(6541):572–575. doi: 10.1038/376572a0. [DOI] [PubMed] [Google Scholar]
  • [31].Goldman-Rakic P.S., Muly I.E.C., Williams G.V. D1 receptors in prefrontal cells and circuits. Brain Res Rev. 2000;31(2–3):295–301. doi: 10.1016/S0165-0173(99)00045-4. [DOI] [PubMed] [Google Scholar]
  • [32].Bergson C., Mrzljak L., Smiley J.F., Pappy M., Levenson R., Goldman-Rakic P.S. Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain. J Neurosci. 1995;15(12):7821–7836. doi: 10.1523/JNEUROSCI.15-12-07821.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Khan Z.U., Gutiérrez A., Martín A., Peñafiel A., Rivera A., de la Calle A. Dopamine D5 receptors of rat and human brain. Neuroscience. 2000;100(4):689–699. doi: 10.1016/S0306-4522(00)00274-8. [DOI] [PubMed] [Google Scholar]
  • [34].Muly E.C., Szigeti K., Goldman-Rakic R.S. D1 receptor in interneurons of macaque prefrontal cortex: distribution and subcellular localization. J. Neurosci. 1998;18(24):10553–10565. doi: 10.1523/JNEUROSCI.18-24-10553.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].He Y., Jin W.Q., Shen Q.X., Chen X.J., Jin G.Z. Expression of dopamine D1 receptor in Sf9 insect cells and agonism of l-12-chloroscoulerine on recombinant D1 receptor. Acta Pharmacol Sin. 2003;24(3):225–229. [PubMed] [Google Scholar]
  • [36].Bordelon-Glausier J.R., Khan Z.U., Muly E.C. Quantification of D1 and D5 dopamine receptor localization in layers I, III, and V of Macaca mulatta prefrontal cortical area 9: coexpression in dendritic spines and axon terminals. J Comp Neurol. 2008;508(6):893–905. doi: 10.1002/cne.21710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [37].Madziva M.T., Edwardson J.M. Trafficking of green fluorescent protein-tagged muscarinic M4 receptors in NG108-15 cells. Eur J Pharmacol. 2001;428(1):9–18. doi: 10.1016/S0014-2999(01)01266-3. [DOI] [PubMed] [Google Scholar]
  • [38].Zeng F.Y., Wess J. Molecular aspects of muscarinic receptor dimerization. Neuropsychopharmacology. 2000;23(4Supplement1):S19–S31. doi: 10.1016/S0893-133X(00)00146-9. [DOI] [PubMed] [Google Scholar]
  • [39].Bloch B., Bernard V., Dumartin B. “In vivo” intraneuronal trafficking of G protein coupled receptors in the striatum: regulation by dopaminergic and cholinergic environment. Biology of the Cell. 2003;95(7):477–488. doi: 10.1016/S0248-4900(03)00080-7. [DOI] [PubMed] [Google Scholar]
  • [40].Ince E., Ciliax B.J., Levey A.I. Differential expression of D1 and D2 dopamine and m4 muscarinic acetylcholine receptor proteins in identified striatonigral neurons. Synapse. 1997;27(4):357–366. doi: 10.1002/(SICI)1098-2396(199712)27:4<357::AID-SYN9>3.0.CO;2-B. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES