Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jan 18;91(2):649–653. doi: 10.1073/pnas.91.2.649

Morphogenic potentials of D2, D3, and D4 dopamine receptors revealed in transfected neuronal cell lines.

B C Swarzenski 1, L Tang 1, Y J Oh 1, K L O'Malley 1, R D Todd 1
PMCID: PMC43006  PMID: 7904756

Abstract

Molecular cloning studies have defined a family of dopamine D2-like receptors (D2, D3, and D4), which are the products of separate genes. Our previous work has shown that stimulation of dopamine D2-like receptors in cultures of fetal cortical neurons increases the extension and branching of neurites. To determine which D2-like receptors possess morphogenic potentials, a clonal mesencephalic cell line (MN9D) was transfected with D2, D3, or D4 receptor subtypes and treated with quinpirole, an agonist of D2-like receptors, and changes in morphological characteristics were quantitated. Stimulation of D2 receptors increased the number and branching of neurites with little effect on neurite extension; stimulation of D3 and D4 receptors increased the branching and extension of neurites. Similar results were found for primary mesencephalic cultures stimulated with quinpirole. These results suggest that the known D2-like receptors have specific developmental roles in regulating neuronal morphogenesis of dopaminergic pathways.

Full text

PDF
649

Images in this article

650Fig. 1
on p.650

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benes F. M., Davidson J., Bird E. D. Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. Arch Gen Psychiatry. 1986 Jan;43(1):31–35. doi: 10.1001/archpsyc.1986.01800010033004. [DOI] [PubMed] [Google Scholar]
  2. Blanton M. G., Lo Turco J. J., Kriegstein A. R. Endogenous neurotransmitter activates N-methyl-D-aspartate receptors on differentiating neurons in embryonic cortex. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8027–8030. doi: 10.1073/pnas.87.20.8027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bunzow J. R., Van Tol H. H., Grandy D. K., Albert P., Salon J., Christie M., Machida C. A., Neve K. A., Civelli O. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature. 1988 Dec 22;336(6201):783–787. doi: 10.1038/336783a0. [DOI] [PubMed] [Google Scholar]
  4. Choi H. K., Won L. A., Kontur P. J., Hammond D. N., Fox A. P., Wainer B. H., Hoffmann P. C., Heller A. Immortalization of embryonic mesencephalic dopaminergic neurons by somatic cell fusion. Brain Res. 1991 Jun 21;552(1):67–76. doi: 10.1016/0006-8993(91)90661-e. [DOI] [PubMed] [Google Scholar]
  5. Choi H. K., Won L., Roback J. D., Wainer B. H., Heller A. Specific modulation of dopamine expression in neuronal hybrid cells by primary cells from different brain regions. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8943–8947. doi: 10.1073/pnas.89.19.8943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chubakov A. R., Gromova E. A., Konovalov G. V., Sarkisova E. F., Chumasov E. I. The effects of serotonin on the morpho-functional development of rat cerebral neocortex in tissue culture. Brain Res. 1986 Mar 26;369(1-2):285–297. doi: 10.1016/0006-8993(86)90537-8. [DOI] [PubMed] [Google Scholar]
  7. Feigenbaum J. J., Yanai J. Normal and abnormal determinants of dopamine receptor ontogeny in the central nervous system. Prog Neurobiol. 1984;23(3):191–225. doi: 10.1016/0301-0082(84)90002-9. [DOI] [PubMed] [Google Scholar]
  8. Fiszman M. L., Zuddas A., Masana M. I., Barker J. L., di Porzio U. Dopamine synthesis precedes dopamine uptake in embryonic rat mesencephalic neurons. J Neurochem. 1991 Feb;56(2):392–399. doi: 10.1111/j.1471-4159.1991.tb08164.x. [DOI] [PubMed] [Google Scholar]
  9. Hauser K. F., McLaughlin P. J., Zagon I. S. Endogenous opioids regulate dendritic growth and spine formation in developing rat brain. Brain Res. 1987 Jul 21;416(1):157–161. doi: 10.1016/0006-8993(87)91509-5. [DOI] [PubMed] [Google Scholar]
  10. Haydon P. G., McCobb D. P., Kater S. B. Serotonin selectively inhibits growth cone motility and synaptogenesis of specific identified neurons. Science. 1984 Nov 2;226(4674):561–564. doi: 10.1126/science.6093252. [DOI] [PubMed] [Google Scholar]
  11. Jeste D. V., Lohr J. B. Hippocampal pathologic findings in schizophrenia. A morphometric study. Arch Gen Psychiatry. 1989 Nov;46(11):1019–1024. doi: 10.1001/archpsyc.1989.01810110061009. [DOI] [PubMed] [Google Scholar]
  12. Lankford K. L., DeMello F. G., Klein W. L. D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4567–4571. doi: 10.1073/pnas.85.12.4567-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LoTurco J. J., Blanton M. G., Kriegstein A. R. Initial expression and endogenous activation of NMDA channels in early neocortical development. J Neurosci. 1991 Mar;11(3):792–799. doi: 10.1523/JNEUROSCI.11-03-00792.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mack K. J., O'Malley K. L., Todd R. D. Differential expression of dopaminergic D2 receptor messenger RNAs during development. Brain Res Dev Brain Res. 1991 Apr 24;59(2):249–251. doi: 10.1016/0165-3806(91)90105-r. [DOI] [PubMed] [Google Scholar]
  15. Mattson M. P., Murrain M., Guthrie P. B., Kater S. B. Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal neuroarchitecture. J Neurosci. 1989 Nov;9(11):3728–3740. doi: 10.1523/JNEUROSCI.09-11-03728.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mattson M. P. Neurotransmitters in the regulation of neuronal cytoarchitecture. Brain Res. 1988 Apr-Jun;472(2):179–212. doi: 10.1016/0165-0173(88)90020-3. [DOI] [PubMed] [Google Scholar]
  17. O'Malley K. L., Harmon S., Tang L., Todd R. D. The rat dopamine D4 receptor: sequence, gene structure, and demonstration of expression in the cardiovascular system. New Biol. 1992 Feb;4(2):137–146. [PubMed] [Google Scholar]
  18. O'Malley K. L., Mack K. J., Gandelman K. Y., Todd R. D. Organization and expression of the rat D2A receptor gene: identification of alternative transcripts and a variant donor splice site. Biochemistry. 1990 Feb 13;29(6):1367–1371. doi: 10.1021/bi00458a003. [DOI] [PubMed] [Google Scholar]
  19. Owens G. C., Johnson R., Bunge R. P., O'Malley K. L. L-3,4-dihydroxyphenylalanine synthesis by genetically modified Schwann cells. J Neurochem. 1991 Mar;56(3):1030–1036. doi: 10.1111/j.1471-4159.1991.tb02025.x. [DOI] [PubMed] [Google Scholar]
  20. Pfefferbaum A., Zipursky R. B., Lim K. O., Zatz L. M., Stahl S. M., Jernigan T. L. Computed tomographic evidence for generalized sulcal and ventricular enlargement in schizophrenia. Arch Gen Psychiatry. 1988 Jul;45(7):633–640. doi: 10.1001/archpsyc.1988.01800310037005. [DOI] [PubMed] [Google Scholar]
  21. Sales N., Martres M. P., Bouthenet M. L., Schwartz J. C. Ontogeny of dopaminergic D-2 receptors in the rat nervous system: characterization and detailed autoradiographic mapping with [125I]iodosulpride. Neuroscience. 1989;28(3):673–700. doi: 10.1016/0306-4522(89)90014-6. [DOI] [PubMed] [Google Scholar]
  22. Sikich L., Hickok J. M., Todd R. D. 5-HT1A receptors control neurite branching during development. Brain Res Dev Brain Res. 1990 Nov 1;56(2):269–274. doi: 10.1016/0165-3806(90)90092-d. [DOI] [PubMed] [Google Scholar]
  23. Sokoloff P., Andrieux M., Besançon R., Pilon C., Martres M. P., Giros B., Schwartz J. C. Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor. Eur J Pharmacol. 1992 Apr 10;225(4):331–337. doi: 10.1016/0922-4106(92)90107-7. [DOI] [PubMed] [Google Scholar]
  24. Sokoloff P., Giros B., Martres M. P., Bouthenet M. L., Schwartz J. C. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990 Sep 13;347(6289):146–151. doi: 10.1038/347146a0. [DOI] [PubMed] [Google Scholar]
  25. Van Tol H. H., Bunzow J. R., Guan H. C., Sunahara R. K., Seeman P., Niznik H. B., Civelli O. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature. 1991 Apr 18;350(6319):610–614. doi: 10.1038/350610a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES