Journal list menu
A primordial dopamine D1-like adenylyl cyclase-linked receptor from Drosophila melanogaster displaying poor affinity for benzazepines
Kim S. Sugamori
Department of Pharmacology, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorLidia L. Demchyshyn
Department of Pharmacology, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorFortunata McConkey
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorMichael A. Forte
Vollum Institute for Advanced Biomedical Research, Portland, OR 97201, USA
Search for more papers by this authorHyman B. Niznik
Department of Psychiatry, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Department of Pharmacology, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorKim S. Sugamori
Department of Pharmacology, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorLidia L. Demchyshyn
Department of Pharmacology, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorFortunata McConkey
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorMichael A. Forte
Vollum Institute for Advanced Biomedical Research, Portland, OR 97201, USA
Search for more papers by this authorHyman B. Niznik
Department of Psychiatry, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Department of Pharmacology, University of Toronto, Toronto, Ont., M5S 1A8, Canada
Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont., M5T 1R8, Canada
Search for more papers by this authorAbstract
We report here the isolation from Drosophila melanogaster of a 2.0 kb cDNA clone encoding a 385 amino acid protein (dDA1) displaying, within putative transmembrane domains, highest amino acid sequence homology (49–53%) to members of the vertebrate dopamine D1-like receptor family. When expressed in either Sf9 or COS-7 cells, dDA1 did not bind the specific D1-like receptor antagonist [3H]SCH-23390 or numerous other dopaminergic, adrenergic or serotoninergic ligands with high affinity. However, like vertebrate dopamine D1-like receptors, dDA1 stimulated the accumulation of cAMP in response to DA (EC50 ∼300 nM) and 6,7-ADTN (EC50∼500 nM). The dopaminergic rank order of potency (DA > NE⪢5-HT) and the lack of stimulation by other possible neurotransmitters (octopamine, tyramine, tryptamine) or DA metabolites (e.g. N-acetyl dopamine) found in Drosophila suggests that this receptor functionally belongs to the dopamine D1-like subfamily. Benzazepines, which characteristically bind to vertebrate dopamine D1-like receptors with high affinity, were relatively poor in stimulating (SKF-38393, SKF-82526; EC50 > 10 μM) dDA1-mediated accumulation of cAMP. Of the numerous compounds tested, a few dopaminergic antagonists inhibited DA-stimulated production of cAMP in a concentration-dependent manner, albeit with considerably reduced affinity, and with the rank order of potency: (+)-butaclamol(K b∼125nM) > SCH-23390(K b∼230nM) > α-flupenthixol (K b ∼ 400 nM) > chlorpromazine ≥ spiperone (K b ∼ 680 nM) ≥ clozapine In situ hybridization revealed that dDA1 receptor mRNA is expressed as a maternal transcript, and at later blastoderm stages is restricted to apical regions of the cortical peripheral cytoplasm. The generation of inter-species D1 receptor chimeras may help to identify those particular sequence-specific motifs or amino acid residues confering high affinity benzazepine receptor interactions.
References
- 1 O. Civelli, J.R. Bunzow, D.K. Grandy, Annu. Rev. Pharmacol. Toxicol., 32, (1993), 281– 307.
- 2 J.A. Gingrich, M.G. Caron, Annu. Rev. Neurosci., 16, (1993), 299– 321.
- 3 H.B. Niznik, H.H.M. Van Tol, J. Psychiatr. Neurosci., 17, (1992), 158– 180.
- 4 D.R. Sibley, F.J. Monsma Jr, Trends Pharmacol. Sci., 13, (1992), 61– 69.
- 5 H. Hall, H.B. Niznik Dopamine Receptors and Transporters (1994), Marcel Dekker New York 3– 35.
- 6 K.S. Sugamori, L.L. Demchyshyn, M. Chung, H.B. Niznik, Proc. Natl. Acad. Sci. USA 91, (1994), 10536– 10540.
- 7 L.L. Demchyshyn, K.S. Sugamori, F.J.S. Lee, S.A. Hamadanizadeh, H.B. Niznik, J. Biol. Chem., 270, (1995), 4005– 4012.
- 8 L.C. Mahan, R.M. Burch, F.J. Monsma Jr, D.R. Sibley, Proc. Natl. Acad. Sci. USA 87, (1990), 2196– 2200.
- 9 A.S. Undie, J. Weinstock, E. Friedman, J. Neurochem., 62, (1994), 2045– 2048.
- 10 J.T. Laitinen, J. Neurochem., 61, (1993), 1461– 1469.
- 11 R.B. Mailman, D.W. Shulz, C.D. Kilts, M.H. Lewis, H. Rollema, S. Wyrick, Psychopharmacol. Bull., 22, (1986), 593– 598.
- 12 J. Arnt, J. Hyttel, C. Sanchez, Eur. J. Pharmacol., 213, (1992), 259– 267.
- 13 S.A. Daly, J.L. Waddington, Psychopharmacol., 113, (1993), 45– 50.
- 14 R.P. Downes, J.L. Waddington, Eur. J. Pharmacol., 234, (1993), 135– 136.
- 15 K.S. Sugamori, H.H.M. Van Tol, H.B. Niznik, H.B. Niznik Dopamine Receptors and Transporters (1994), Marcel Dekker New York 103– 129.
- 16 S. Weiss, G.I. Drummond, Mol. Pharmacol., 20, (1981), 592– 597.
- 17 D. Sonetti, C. Biondi, M.E. Ferretti, A. Portolan, M. Brunelli, Neurochem. Int., 11, (1987), 119– 126.
- 18 G. Venturini, Comp. Biochem. Physiol., 105C, (1993), 297– 301.
- 19 D.W. Ali, I. Orchard, Biogenic Amines, 10, (1994), 195– 212.
- 20 P. Witz, N. Amlaiky, J.-L. Plassat, L. Maroteaux, E. Borrelli, R. Hen, Proc. Natl. Acad. Sci. USA 87, (1990), 8940– 8944.
- 21 F. Saudou, U. Boschert, N. Amlaiky, J.-L. Plassat, R. Hen, EMBO J., 11, (1992), 7– 17.
- 22 F. Saudou, N. Amlaiky, J.-L. Plassat, E. Borelli, R. Hen, EMBO J., 9, (1990), 3611– 3617.
- 23 S. Arakawa, J.D. Gocayne, W.R. McCombie, D.A. Urquhart, L.M. Hall, D.A. Fraser, J.C. Venter, Neuron, 2, (1990), 343– 354.
- 24 V. Budnik, K. White, J. Comp. Neurol., 268, (1988), 400– 413.
- 25 D.R. Nassel, K. Elekes, Cell Tissue Res., 267, (1992), 147– 167.
- 26 B.L. Tempel, M.S. Livingstone, W.G. Quinn, Proc. Natl. Acad. Sci. USA 81, (1984), 3577– 3581.
- 27 R.L. Davis, Neuron, 11, (1993), 1– 14.
- 28 K.J. Fryxell, H.B. Niznik Dopamine Receptors and Transporters (1994), Marcel Dekker New York 237– 263.
- 29 R.K. Sunahara, H.-C. Guan, B.F. O'Dowd, P. Seeman, L.G. Laurier, G. Ng, S.R. George, J. Torchia, H.H.M. Van Tol, H.B. Niznik, Nature, 350, (1991), 614– 619.
- 30 Z.B. Pristupa, J.M. Wilson, B.J. Hoffman, S.J. Kish, H.B. Niznik, Mol. Pharmacol., 45, (1994), 125– 135.
- 31 R.K. Sunahara, H.B. Niznik, D.M. Weiner, T.M. Stormann, M.R. Brann, J.L. Kennedy, J.E. Gelernter, R. Rozmahel, Y. Yang, Y. Israel, P. Seeman, B.F. O'Dowd, Nature, 347, (1990), 80– 83.
- 32 F. Quan, W.J. Wolfgang, M.A. Forte, Proc. Natl. Acad. Sci. USA 90, (1993), 4236– 4240.
- 33 S.M. Mount, C. Burks, G. Hertz, G.D. Stormo, O. White, C. Fields, Nucleic Acids Res., 20, (1992), 4255– 4262.
- 34 M. Kozak, Cell, 44, (1986), 283– 292.
- 35 R.A.F. Dixon, I.S. Sigal, M.R. Candelore, R.B. Register, W. Scattergood, W. Rands, C.D. Strader, EMBO J., 6, (1987), 3269– 3275.
- 36 N.J. Pollock, A.M. Manelli, C.W. Hutchins, M.E. Steffey, R.G. MacKenzie, D.E. Frail, J. Biol. Chem., 267, (1992), 17780– 17786.
- 37 C.D. Strader, R.A.F. Dixon, A.H. Cheung, M.R. Candelore, A.D. Blake, I.S. Sigal, J. Biol. Chem., 262, (1987), 16439– 16443.
- 38 H.M. Dalman, R.R. Neubig, J. Biol. Chem., 266, (1991), 11025– 11029.
- 39 L.M. Luttrell, J. Ostrowski, S. Cotecchia, H. Kendall, R.J. Lefkowitz, Science, 259, (1993), 1453– 1457.
- 40 B.E. Hawes, L.M. Luttrell, S.T. Exum, R.J. Lefkowitz, J. Biol. Chem., 269, (1994), 15776– 15785.
- 41 T. Okamoto, I. Nishimoto, J. Biol. Chem., 267, (1992), 8342– 8346.
- 42 T. Namba, Y. Sugimoto, M. Negishi, A. Irie, F. Ushikubi, A. Kakizuka, S. Ito, A. Ichikawa, A. Narumiya, Nature, 365, (1993), 166– 170.
- 43 K.S. Sugamori, R.K. Sunahara, H.-C. Guan, A.G.M. Bulloch, C.P. Tensen, P. Seeman, H.B. Niznik, H.H.M. Van Tol, Proc. Natl. Acad. Sci. USA 90, (1993), 11– 15.
- 44 S. Weiss, J.I. Goldberg, K. Lukowiak, G.I. Drummond, J. Comp. Physiol. B, 156, (1985), 57– 65.
- 45 S. Lazareno, N.J.M. Birdsall, Trends Pharmacol. Sci., 14, (1993), 237– 239.
- 46 P.H. Andersen, J.A. Gingrich, M.D. Bates, A. Dearry, P. Falardeau, S.E. Senogles, M.G. Caron, Trends Pharmacol. Sci., 11, (1990), 231– 236.
- 47 K.L. Lankford, F.G. Demello, W.L. Klein, Proc. Natl. Acad. Sci. USA 85, (1988), 2839– 2843.
- 48 P.D.S. Rodrigues, J.E. Dowling, Proc. Natl. Acad. Sci. USA 87, (1990), 9693– 9697.
- 49 J.E. Dowling, H.B. Niznik Dopamine Receptors and Transporters (1994), Marcel Dekker New York 37– 57.
- 50 L. Davis, D. Ish-Horowicz, Cell, 67, (1991), 927– 940.
- 51 M. Xu, R. Moratalla, L.H. Gold, N. Hiroi, G.F. Kob, A.M. Graybiel, S. Tonegawa, Cell, 79, (1994), 729– 742.
- 52 F. Gotzes, S. Balfanz, A. Baumann, Receptors Channels, 2, (1994), 131– 141.
- 53 Q.Y. Zhou, D.K. Grandy, L. Thambi, J.A. Kushner, H.H.M. Van Tol, R. Cone, D. Pribnow, J. Salon, J.R. Bunzow, O. Civelli, Nature, 347, (1990), 76– 80.
- 54 A.G. Dearry, J. Gingrich, P. Falardeau, R.T. Fremeau, M.D. Bates, M.G. Caron, Nature, 347, (1990), 72– 76.
- 55 C.A. Machida, R.P. Searles, V. Nipper, J.A. Brown, L.B. Kozell, K.A. Neve, Mol. Pharmacol., 41, (1992), 652– 659.
- 56 S.R. Nash, N. Godinot, M.G. Caron, Mol. Pharmacol., 44, (1993), 918– 925.
- 57 D.E. Frail, A.M. Manelli, D.G. Witte, C.W. Lin, M.E. Steffey, R.G. Mackenzie, Mol. Pharmacol., 44, (1993), 1113– 1118.
- 58 R.L. Weinshank, N. Adham, M. Macchi, M.A. Olsen, T.A. Branchek, P.R. Hartig, J. Biol. Chem., 266, (1991), 22427– 22435.
- 59 D.K. Grandy, Y. Zhang, C. Bouvier, Q.-Y. Zhou, R.A. Johnson, L. Allen, K. Buck, J.R. Bunzow, J. Salon, O. Civelli, Proc. Natl. Acad. Sci. USA 88, (1991), 9175– 9179.
- 60 M. Tiberi, K.R. Jarvie, C. Silvia, P. Falardeau, J.A. Gingrich, N. Godinot, L. Bertrand, T.L. Yang-Feng, R.T.J. Fremeau, M.G. Caron, Proc. Natl. Acad. Sci. USA 88, (1991), 7491– 7495.