Skip to main content
SpringerLink
Log in

The evolutionary divergence of neurotransmitter receptors and second-messenger pathways

  • Articles
  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Members of the superfamily of G-protein-coupled neurotransmitter receptors have a conserved secondary structure, a moderate and reasonably steady rate of sequence change, and usually lack introns within the coding sequence. These properties are advantageous for evolutionary studies. The duplication and divergence of the genes in this gene family led to the formation of distinct neurotransmitter pathways and may have facilitated the evolution of complex nervous systems. I have analyzed this evolutionary divergence by quantitative multiple sequence alignment, bootstrap resampling, and statistical analysis of 49 adrenergic, muscarinic cholinergic, dopamine, and octopamine receptor sequences from 12 animal species. The results indicate that the first event to occur within this gene family was the divergence of the catecholamine receptors from the muscarinic acetylcholine receptors, which occurred prior to the divergence of the arthropod and vertebrate lineages. Subsequently, the ability to activate specific second-messenger pathways diverged independently in both the muscarinic and the catecholamine receptors. This appears to have occurred after the divergence of the arthropod and vertebrate lineages but before the divergence of the avian and mammalian lineages. However, the second-messenger pathways activated by adrenergic and dopamine receptors did not diverge independently. Rather, the ability of the catecholamine receptors to bind to specific ligands, such as epinephrine, norepinephrine, dopamine, or octopamine, was repeatedly modified in evolutionary history, and in some cases was modified after the divergence of the second-messenger pathways.

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

  • Akiba I, Kubo T, Maeda A, Bujo H, Nakai J, Mishina M, Numa S (1988) Primary structure of porcine muscarinic acetylcholine receptor III and antagonist binding studies. FEBS Lett 235:257–261

    Google Scholar 

  • Allard WJ, Sigal IS, Dixon RAF (1987) Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor. Nucleic Acids Res 15:10604

    Google Scholar 

  • Allen JM, Baetge EE, Abrass IB, Palmiter RD (1988) Isoproterenol response following transfection of the mouse beta2-adrenergic receptor gene into Y1 cells. EMBO J 7:133–138

    Google Scholar 

  • Arakawa S, Gocayne JD, McCombie WR, Urquhart DA, Hall LM, Fraser CM, Venter JC (1990) Cloning, localization, and permanent expression of a Drosophila octopamine receptor. Neuron 4:343–354

    Google Scholar 

  • Bonner TI, Buckley NJ, Young AC, Brann MR (1987) Identification of a family of muscarinic acetylcholine receptor genes. Science 237: 527–532

    CAS  PubMed  Google Scholar 

  • Bonner TI, Young AC, Brann MR, Buckley NJ (1988) Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. Neuron 1:403–410

    Google Scholar 

  • Bonner TI (1989) The molecular basis of muscarinic receptor diversity. Trends Neurosci 12:148–151

    Google Scholar 

  • Braun T, Schofield PR, Shivers BD, Pritchett DB, Seeburg PH (1987) A novel subtype of muscarinic receptor identified by homology screening. Biochem Biophys Res Commun 149:125–132

    Google Scholar 

  • Bruno JF, Whittaker J, Song J, Berelowitz M (1991) Molecular cloning and sequencing of a cDNA encoding a human alpha 1A adrenergic receptor. Biochem Biophys Res Commun 179:1485–1490

    Google Scholar 

  • Buckland PR, Hill RM, Tidmarsh SF, McGuffin P (1990) Primary structure of the rat beta-2 adrenergic receptor gene. Nucleic Acids Res 18:682

    Google Scholar 

  • Budnik V, White K (1988) Catecholamine-containing neurons in Drosophila melanogaster: distribution and development. J Comp Neurol 268:400–413

    CAS  PubMed  Google Scholar 

  • Bunzow JR, Van Tol HHM, Grandy DK, Albert P, Salon J, Christie M, Machida CA, Neve KA, Civelli O (1988) Cloning and expression of a rat D(2) dopamine receptor cDNA. Nature 336:783–787

    Google Scholar 

  • Carulli JP, Hartl DL (1992) Variable rates of evolution among Drosophila opsin genes. Genetics 132:193–204

    Google Scholar 

  • Chalberg SC, Duda T, Rhine JA, Sharma RK (1990) Molecular cloning, sequencing and expression of an alpha2-adrenergic receptor complementary DNA from rat brain. Mol Cell Biochem 97:161–172

    Google Scholar 

  • Chang AC, Ho TF, Chang NC (1990) In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans. Biochem Biophys Res Commun 172:817–823

    Google Scholar 

  • Chapman CG, Browne MJ (1990) Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification. Nucleic Acids Res 18:2191

    Google Scholar 

  • Chhajlani V, Rangel N, Uhlen S, Wikberg JES (1991) Identification of an additional gene belonging to the alpha(2) adrenergic receptor family in the human genome by PCR. FEBS Lett 280:241–244

    Google Scholar 

  • Chio CL, Hess GF, Graham RS, Huff RM (1990) A second molecular form of D2 dopamine receptor in rat and bovine caudate nucleus. Nature 343:266–269

    Google Scholar 

  • Chung FZ, Lentes KU, Gocayne J, Fitzgerald M, Robinson D, Kerlavage AR, Fraser CM, Venter JC (1987) Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinie receptors. FEBS Lett 211:200–206

    Google Scholar 

  • Cotecchia S, Schwinn DA, Randall RR, Lefkowitz RJ, Caron MG, Kobilka BK (1988) Molecular cloning and expression of the cDNA for the hamster alpha- 1-adrenergic receptor. Proc Natl Acad Sci USA 85:7159–7163

    Google Scholar 

  • dal Toso R, Sommer B, Ewert M, Herb A, Pritchett DB, Bach A, Shivers BD, Seeburg PH (1989) The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J 8:4025–4034

    Google Scholar 

  • Deary A, Gingrich JA, Falardeau P, Fremeau RT Jr, Bates MD, Caron MG (1990) Molecular cloning and expression of the gene for a human D(1) dopamine receptor. Nature 347:72–76

    Google Scholar 

  • Dixon RAF, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford RA, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ, Strader CD (1986) Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature 321:75–79

    Google Scholar 

  • Efstratiadis A, Posakony JW, Maniatis T, Lawn RM, O'Connell C, Spritz RA, DeRiel JK, Forget BG, Weissman SM, Slightom JL, Blechl AE, Smithies O, Baralle FE, Shoulders CC, Proudfoot NJ (1980) The structure and evolution of the human beta-globin gene family. Cell 21:653–668

    Google Scholar 

  • Eldefrawi AT (1976) The acetylcholine receptor and its interactions with insecticides. In: Wilkinson CF (ed) Insecticide biochemistry and physiology. Plenum Press, New York, pp 297–326

    Google Scholar 

  • Emorine LJ, Marullo S, Delavier-Klutchko C, Kaveri SV, Durieu-Trautmann O, Strosberg AD (1987) Structure of the gene for human beta-2-adrenergic receptor: expression and promoter characterization. Proc Natl Acad Sci USA 84:6995–6999

    Google Scholar 

  • Emorine LJ, Marullo S, Briend-Sutren MM, Patey G, Tate K, Delavier-Klutchko C, Strosberg AD (1989) Molecular characterization of the human beta-3-adrenergic receptor. Science 245:1118–1121

    Google Scholar 

  • Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791

    Google Scholar 

  • Felsenstein J (1988) Phylogenies from molecular sequences: inference and reliability. Annu Rev Genet 22:521–565

    Google Scholar 

  • Feng DF, Doolittle RF (1987) Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol 25:351–360

    Google Scholar 

  • Feng DF, Doolittle RF (1990) Progressive alignment and phylogenetic tree construction of protein sequences. Methods Enzymol 183:375–387

    Google Scholar 

  • Flordellis CS, Handy DE, Bresnahan MR, Zannis VI, Gavras H (1991) Cloning and expression of a rat brain alpha-2beta-adrenergic receptor. Proc Natl Acad Sci USA 88:1019–1023

    Google Scholar 

  • Fraser CM, Arakawa S, McCombie WR, Venter JC (1989) Cloning, sequence analysis, and permanent expression of a human alpha2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation. J Biol Chem 264:11754–11761

    Google Scholar 

  • Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK (1987) Cloning of the cDNA for the human beta-1-adrenergic receptor. Proc Natl Acad Sci USA 84:7920–7924

    Google Scholar 

  • Fryxell KJ, Meyerowitz EM (1991) The evolution of rhodopsins and neurotransmitter receptors. J Mol Evol 33:367–378

    Google Scholar 

  • Fryxell KJ (1994) The evolution of the dopamine receptor gene family. In: Niznik HB (ed) Dopamine receptors and transporters. Marcel Dekker, New York, pp 237–260

    Google Scholar 

  • Fukuto TR (1979) Effect of structure on the interaction of organophosphorus and carbamate esters with acetylcholinesterase. In: Narahashi T (ed) Neurotoxicology of insecticides and pheromones. Plenum Press, New York, pp 277–295

    Google Scholar 

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

    Google Scholar 

  • Gocayne J, Robinson DA, FitzGerald MG, Chung FZ, Kerlavage AR, Lentes KU, Lai J, Wang CD, Fraser CM, Venter JC (1987) Primary structure of rat cardiac beta-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: further evidence for a multigene family. Proc Natl Acad Sci USA 84:8296–8300

    Google Scholar 

  • Graham A, Papalopulu N, Krumlauf R (1989) The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell 57:367–378

    Google Scholar 

  • Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC, Civelli O (1989) Cloning of the cDNA and gene for a human D-2 dopamine receptor. Proc Natl Acad Sci USA 86:9762–9766

    Google Scholar 

  • Greenspan RJ (1980) Mutations of choline acetyltransferase and associated neural defects in Drosophila melanogaster. J Comp Physiol 137:83–92

    Google Scholar 

  • Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ Jr, Limbird LE (1990) Cloning, sequencing, and expression of the gene encoding the porcine alpha-2-adrenergic receptor. Allosteric modulation by Na(+), H(+), and amiloride analogs. J Biol Chem 265:17307–17317

    Google Scholar 

  • Hargrave PA (1991) Seven-helix receptors. Curr Opin Struct Biol 1: 575–581

    Google Scholar 

  • Hermans-Borgmeyer I, Zopf D, Ryseck RP, Hovemann B, Betz H, Gundelfinger ED (1986) Primary structure of a developmentally regulated nicotinic acetylcholine receptor protein from Drosophila. EMBO J 5:1503–1508

    Google Scholar 

  • Jones SW, Sudershan P, O'Brien RD (1979) Interaction of insecticides with acetylcholine receptors. In: Narahashi T (ed) Neurotoxicology of insecticides and pheromones. Plenum Press, New York, pp 259–275

    Google Scholar 

  • Kobilka BK, Dixon RAF, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ (1987a) cDNA for the human beta-2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc Natl Acad Sci USA 84:46–50

    Google Scholar 

  • Kobilka BK, Frielle T, Dohlman HG, Bolanowski MA, Dixon RAF, Keller P, Caron MG, Lefkowitz RJ (1987b) Delineation of the intronless nature of the genes for the human and hamster beta-2-adrenergic receptor and their putative promoter regions. J Biol Chem 262:7321–7327

    Google Scholar 

  • Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW (1987c) Cloning, sequencing, and expression of the gene coding for the human platelet alpha-2-adrenergic receptor. Science 238:650–656

    CAS  PubMed  Google Scholar 

  • Kubo T, Fukuda K, Mikami A, Maeda A, Takahashi H, Mishina M, Haga T, Haga K, Ichiyama A, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S (1986a) Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature 323:411–416

    Google Scholar 

  • Kubo T, Maeda A, Sugimoto K, Akiba I, Mikami A, Takahashi H, Haga T, Haga K, Ichiyama A, Kangawa K, Matsuo H, Hirose T, Numa S (1986b) Primary structure of porcine cardiac muscarinic acetylcholine receptor deduced from the cDNA sequence. FEBS Lett 209:367–372

    Google Scholar 

  • Kurtenbach E, Curtis CAM, Pedder EK, Aitken A, Harris ACM, Hulme EC (1990) Muscarinic acetylcholine receptors. Peptide sequencing identifies residues involved in antagonist binding and disulfide bond formation. J Biol Chem 265:13702–13708

    Google Scholar 

  • Lanier SM, Downing S, Duzic E, Homey CJ (1991) Isolation of rat genomic clones encoding subtypes of the alpha-2-adrenergic receptor. Identification of a unique receptor subtype. J Biol Chem 266: 10470–10478

    Google Scholar 

  • Lewin B (1990) Genes IV. Oxford University Press, New York

    Google Scholar 

  • Liao CF, Themmen APN, Joho R, Barberis C, Birnbaumer M, Birnbaumer L (1989) Molecular cloning and expression of a fifth muscarinic acetylcholine receptor. J Biol Chem 264:7328–7337

    Google Scholar 

  • Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons MJ, Dumont JE, Vassart G (1989) Selective amplification and cloning of four new members of the G protein-coupled receptor family. Science 244:569–572

    Google Scholar 

  • Livingstone MS, Tempel BL (1983) Genetic dissection of monoamine neurotransmitter synthesis in Drosophila. Nature 303:67–70

    Google Scholar 

  • Lomasney JW, Cotecchia S, Lorenz W, Leung WY, Schwinn DA, Yang-Feng TL, Brownstein M, Lefkowitz RJ, Caron MG (1991) Molecular cloning and expression of the cDNA for the alpha-1A-adrenergic receptor. The gene for which is located on human chromosome 5. J Biol Chem 266:6365–6369

    Google Scholar 

  • Machida CA, Bunzow JR, Searles RP, Van Tol H, Tester B, Neve KA, Teal P, Nipper V, Civelli O (1990) Molecular cloning and expression of the rat beta-1-adrenergic receptor gene. J Biol Chem 265: 12960–12965

    Google Scholar 

  • Mack KJ, Todd RD, O'Malley KL (1991) The mouse dopamine D2A receptor gene: sequence homology with the rat and human genes and expression of alternative transcripts. J Neurochem 57:795–801

    Google Scholar 

  • Martens GJM, Molhuizen HOF, Groeneveld D, Roubos EW (1991) Cloning and sequence analysis of brain cDNA encoding a Xenopus D(2) dopamine receptor. FEBS Lett 281:85–89

    Google Scholar 

  • Miller JC, Wang Y, Filer D (1990) Identification by sequence analysis of a second rat brain cDNA encoding the dopamine (D2) receptor. Biochem Biophys Res Commun 166:109–112

    Google Scholar 

  • Minneman KP, Pittman RN, Molinoff PB (1981) Beta-adrenergic receptor subtypes: properties, distribution, and regulation. Annu Rev Neurosci 4:419–461

    Google Scholar 

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

    Google Scholar 

  • Monsma FJ Jr, Mahan LC, McVittie LD, Gerfen CR, Sibley DR (1990) Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. Proc Natl Acad Sci USA 87:6723–6727

    Google Scholar 

  • Montmayeur JP, Bausero P, Amlaiky N, Maroteaux L, Hen R, Borrelli E (1991) Differential expression of the mouse D(2) dopamine receptor isoforms. FEBS Lett 278:239–243

    Google Scholar 

  • Nakada MT, Haskell KM, Ecker DJ, Stadel JM, Crooke ST (1989) Genetic regulation of beta(2)-adrenergic receptors in 3T3-L1 fibroblasts. Biochem J 260:53–59

    Google Scholar 

  • Nathans J, Thomas D, Hogness DS (1986) Molecular genetics of human color vision: the genes encoding blue, green and red pigments. Science 232:193–202

    Google Scholar 

  • Niznik HB, Van Tol HHM (1992) Dopamine receptor genes: new tools for molecular psychiatry. J Psychiatr Neurosci 17:1–23

    Google Scholar 

  • O'Brien RD (1976) Acetylcholinesterase and its inhibition. In: Wilkinson CF (ed) Insecticide biochemistry and physiology. Plenum Press, New York, pp 271–296

    Google Scholar 

  • O'Dowd BF, Lefkowitz RJ, Caron MG (1989) Structure of the adrenergic and related receptors. Annu Rev Neurosci 12:67–83

    Google Scholar 

  • O'Dowd BF, Nguyen T, Tirpak A, Jarvie KR, Israel Y, Seeman P, Niznik HB (1990) Cloning of two additional catecholamine receptors from rat brain. FEBS Lett 262:8–12

    Google Scholar 

  • Onai T, FitzGerald MG, Arakawa S, Gocayne JD, Urquhart DA, Hall LM, Fraser CM, McCombie WR, Venter JC (1989) Cloning, sequence analysis and chromosome localization of a Drosophila muscarinic acetylcholine receptor. FEBS Lett 255:219–225

    Google Scholar 

  • Patterson PH (1992) Process outgrowth and the specificity of connections. In: Hall ZW (ed) An introduction to molecular neurobiology. Sinauer Associates, Sunderland, MA, pp 388–427

    Google Scholar 

  • Peralta EG, Winslow JW, Peterson GL, Smith DH, Ashkenazi A, Ramachandran J, Schimerlik MI, Capon DJ (1987a) Primary structure and biochemical properties of an M-2 muscarinic receptor. Science 236:600–605

    Google Scholar 

  • Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ (1987b) Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J 6:3923–3929

    Google Scholar 

  • Plapp FW (1976) Biochemical genetics of insecticide resistance. Annu Rev Entomol 21:179–197

    Google Scholar 

  • Rao DD, McKelvy J, Kebabian J, MacKenzie RG (1990) Two forms of the rat D(2) dopamine receptor as revealed by the polymerase chain reaction. FEBS Lett 263:18–22

    Google Scholar 

  • Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK (1988) Cloning and expression of a human kidney cDNA for an alpha-2-adrenergic receptor subtype. Proc Natl Acad Sci USA 85:6301–6305

    CAS  PubMed  Google Scholar 

  • Robakis NK, Mohamadi M, Fu DY, Sambamurti K, Refolo LM (1990) Human retina D2 receptor cDNAs have multiple polyadenylation sites and differ from a pituitary clone at the 5′ non-coding region. Nucleic Acids Res 18:1299

    Google Scholar 

  • Ross EM (1992) G proteins and receptors in neuronal signaling. In: Hall ZW (ed) An introduction to molecular neurobiology. Sinauer Associates, Sunderland, MA, pp 181–206

    Google Scholar 

  • Schofield PR, Rhee LM, Peralta EG (1987) Primary structure of the human beta-adrenergic receptor gene. Nucleic Acids Res 15:3636

    Google Scholar 

  • Schwinn DA, Lomasney JW, Lorenz W, Szklut PJ, Fremeau RT Jr, Yang-Feng TL, Caron MG, Lefkowitz RJ, Cotecchia S (1990) Molecular cloning and expression of the cDNA for a novel alpha-1-adrenergic receptor subtype. J Biol Chem 265:8183–8189

    Google Scholar 

  • Selbie LA, Hayes G, Shine J (1989) The major dopamine D2 receptor: molecular analysis of the human D2-A subtype. DNA 8:683–689

    Google Scholar 

  • Shapiro RA, Scherer NM, Habecker BA, Subers EM, Nathanson NM (1988) Isolation, sequence, and functional expression of the mouse M1 muscarinic acetylcholine receptor gene. J Biol Chem 263:18397–18403]

    Google Scholar 

  • Shapiro RA, Scherer NM, Habecker BA, Subers EM, Nathanson NM (1989a) Erratum, correct translation of residue 119. J Biol Chem 264:6596

    Google Scholar 

  • Shapiro RA, Wakimoto BT, Subers EM, Nathanson NM (1989b) Characterization and functional expression in mammalian cells of genomic and cDNA clones encoding a Drosophila muscarinic acetylcholine receptor. Proc Natl Acad Sci USA 86:9039–9043

    Google Scholar 

  • Shimomura H, Terada A (1990) Primary structure of the rat beta-1 adrenergic receptor gene. Nucleic Acids Res 18:4591

    Google Scholar 

  • Simon MI, Strathmann MP, Gautam N (1991) Diversity of G proteins in signal transduction. Science 252:802–808

    Google Scholar 

  • Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D(3)) as a target for neuroleptics. Nature 347:146–151

    Google Scholar 

  • Stormann TM, Gdula DC, Weiner DM, Brann MR (1990) Molecular cloning and expression of a dopamine D2 receptor from human retina. Mol Pharmacol 37:1–6

    Google Scholar 

  • Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy JL, Gelerner JE, Rozmahel R, Yang Y, Israel Y, Seeman P, O'Dowd BF (1990) Human dopamine D(1) receptor encoded by an intronless gene on chromosome 5. Nature 347:80–83

    Google Scholar 

  • Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HHM, Niznik HB (1991) Cloning of the gene for a human dopamine D(5) receptor with higher affinity for dopamine than D(1). Nature 350:614–619

    Google Scholar 

  • Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT Jr, Caron MG (1991) Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D-1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D-1A receptor. Proc Natl Acad Sci USA 88:7491–7495

    Google Scholar 

  • Tietje KM, Goldman PS, Nathanson NM (1990) Cloning and functional analysis of a gene encoding a novel muscarinic acetylcholine receptor expressed in chick heart and brain. J Biol Chem 265:2828–2834

    Google Scholar 

  • Tietje KM, Nathanson NM (1991) Embryonic chick heart expresses multiple muscarinic acetylcholine receptor subtypes. Isolation and characterization of a gene encoding a novel m2 muscarinic acetylcholine receptor with high affinity for pirenzepine. J Biol Chem 266:17382–17387

    Google Scholar 

  • Van Tol HHM, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D(4) receptor with high affinity for the antipsychotic clozapine. Nature 350:610–614

    Article  PubMed  Google Scholar 

  • Voigt MM, Kispert J, Chin H (1990) Sequence of a rat brain cDNA encoding an alpha-1B adrenergic receptor. Nucleic Acids Res 18: 1053

    Google Scholar 

  • Voigt MM, McCune SK, Kanterman RY, Felder CC (1991) The rat alpha(2)-C4 adrenergic receptor gene encodes a novel pharmacologic subtype. FEBS Lett 278:45–50

    Google Scholar 

  • Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA, Hartig PR (1990) Cloning, expression, and pharmacological characterization of a human alpha-2B-adrenergic receptor. Mol Pharmacol 38:681–688

    Google Scholar 

  • Wright TRF (1987) The genetics of biogenic amine metabolism, sclerotization, and melanization in Drosophila melanogaster. Adv Genet 24:127–222

    Google Scholar 

  • Yarden Y, Rodriguez H, Wong SKF, Brandt DR, May DC, Burnier J, Harkins RN, Chen EY, Ramachandran J, Ullrich A, Ross EM (1986) The avian beta-adrenergic receptor: primary structure and membrane topology. Proc Natl Acad Sci USA 83:6795–6799

    Google Scholar 

  • Zeng D, Harrison JK, D'Angelo DD, Barber CM, Tucker AL, Lu Z, Lynch KR (1990) Molecular characterization of a rat alpha-2beta-adrenergic receptor. Proc Natl Acad Sci USA 87:3102–3106

    Google Scholar 

  • Zhou QY, Grandy DK, Thambi L, Kushner JA, Van Tol HHM, Cone R, Pribnow D, Salon J, Bunzow JR, Civelli O (1990) Cloning and expression of human and rat D(1) dopamine receptors. Nature 347: 76–80

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, University of California, 92521-0427, Riverside, CA, USA

    Karl J. Fryxell

Authors
  1. Karl J. Fryxell
    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

Fryxell, K.J. The evolutionary divergence of neurotransmitter receptors and second-messenger pathways. J Mol Evol 41, 85–97 (1995). https://doi.org/10.1007/BF00174044

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00174044

Key words

Search

Navigation