Impact of GPCRs in clinical medicine: Monogenic diseases, genetic variants and drug targets

Biochimica et Biophysica Acta - Biomembranes

Volumn 1768, Issue 4, 2007, Pages 994-1005

  Insel, Paul A ^a   Tang, Chih Min ^a   Hahntow, Ines ^b   Michel, Martin C ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

GPCR mutation; Human disease; Nephrogenic diabetes insipidus; Retinitis pigmentosa

Indexed keywords

ADRENERGIC RECEPTOR; ALPHA 1 ADRENERGIC RECEPTOR BLOCKING AGENT; ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; ATENOLOL; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIMIMETIC AGENT; CARVEDILOL; CLOZAPINE; DOPAMINE RECEPTOR; DOPAMINE RECEPTOR BLOCKING AGENT; DOPAMINE RECEPTOR STIMULATING AGENT; FLUVOXAMINE; FORMOTEROL; G PROTEIN COUPLED RECEPTOR; HALOPERIDOL; LEVODOPA; LOSARTAN; METOPROLOL; PROPRANOLOL; SALBUTAMOL; SALMETEROL; SEROTONIN ANTAGONIST; SEROTONIN RECEPTOR; TAMSULOSIN; TERBUTALINE;

AMINO ACID SEQUENCE; ANGINA PECTORIS; ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL MEDICINE; CONGESTIVE HEART FAILURE; DEPRESSION; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG TARGETING; ENDOCRINE DISEASE; ESSENTIAL HYPERTENSION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC VARIABILITY; HEART INFARCTION; HUMAN; HYPERTENSION; ISCHEMIC HEART DISEASE; KIDNEY INJURY; MONOGENIC DISORDER; NONHUMAN; OBSTRUCTIVE AIRWAY DISEASE; PARKINSON DISEASE; PREMATURE LABOR; PRIORITY JOURNAL; PROSTATE HYPERTROPHY; PROTEIN FUNCTION; PROTEIN POLYMORPHISM; REVIEW; SCHIZOPHRENIA; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; TARDIVE DYSKINESIA; UNSPECIFIED SIDE EFFECT; WEIGHT GAIN;

ALLELES; GENETIC DISEASES, INBORN; HUMANS; MUTATION; RECEPTORS, G-PROTEIN-COUPLED;

EID: 33947379232     PISSN: 00052736     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbamem.2006.09.029     Document Type: Review

References (128)

1. Kirstein S.L., and Insel P.A. Autonomic nervous system pharmacogenomics: a progress report. Pharmacol. Rev. 56 (2004) 31-52
2. Thompson M.D., Burnham W.M., and Cole D.E. The G protein-coupled receptors: pharmacogenetics and disease. Crit. Rev. Clin. Lab. Sci. 42 (2005) 311-392
3. Tang C.M., and Insel P.A. Genetic variation in G-protein-coupled receptors-Consequences for G-protein-coupled receptors as drug targets. Expert Opin. Ther. Targets 9 (2005) 1247-1265
4. Tao Y.X. Inactivating mutations of G protein-coupled receptors and diseases: Structure-function insights and therapeutic implications. Pharmacol. Ther. 111 (2006) 946-973
5. Spiegel A.M., and Weinstein L.S. Inherited diseases involving G proteins and G protein-coupled receptors. Annu. Rev. Med. 55 (2004) 27-39
6. Schoneberg T., Schulz A., Biebermann H., Hermsdorf T., Rompler H., and Sangkuhl K. Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol. Ther. 104 (2004) 173-206
7. Nature Reviews Drug Discovery GPCR Questionnaire Participants. The state of GPCR research in 2004. Nat. Rev., Drug Discov. 3 (2004) 575-577
8. Liebmann C. G protein-coupled receptors and their signaling pathways: classical therapeutical targets susceptible to novel therapeutic concepts. Curr. Pharm. Des. 10 (2004) 1937-1958
9. Rana B.K., and Insel P.A. Receptor databases and computational websites for ligand binding. Methods Mol. Biol. 306 (2005) 1-15
10. Fredriksson R., and Schioth H.B. The repertoire of G-protein-coupled receptors in fully sequenced genomes. Mol. Pharmacol. 67 (2005) 1414-1425
11. Fain G.L. Why photoreceptors die (and why they don't). Bioessays 28 (2006) 344-354
12. Sands J.M., and Bichet D.G. Nephrogenic diabetes insipidus. Ann. Intern. Med. 144 (2006) 186-194
13. Wuller S., Wiesner B., Loffler A., Furkert J., Krause G., Hermosilla R., Schaefer M., Schulein R., Rosenthal W., and Oksche A. Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors. J. Biol. Chem. 279 (2004) 47254-47263
14. Tfelt-Hansen J., and Brown E.M. The calcium-sensing receptor in normal physiology and pathophysiology: a review. Crit. Rev. Clin. Lab. Sci. 42 (2005) 35-70
15. Thakker R.V. Diseases associated with the extracellular calcium-sensing receptor. Cell Calcium 35 (2004) 275-282
16. Schott M., Scherbaum W.A., and Morgenthaler N.G. Thyrotropin receptor autoantibodies in Graves' disease. Trends Endocrinol. Metab. 16 (2005) 243-248
17. Davies T.F., Ando T., Lin R.Y., Tomer Y., and Latif R. Thyrotropin receptor-associated diseases: from adenomata to Graves disease. J. Clin. Invest. 115 (2005) 1972-1983
18. Kierszenbaum F. Where do we stand on the autoimmunity hypothesis of Chagas disease?. Trends Parasitol. 21 (2005) 513-516
19. Wallukat G., Nissen E., Morwinski R., and Muller J. Autoantibodies against the beta- and muscarinic receptors in cardiomyopathy. Herz 25 (2000) 261-266
20. Jahns R., Boivin V., and Lohse M.J. beta(1)-Adrenergic receptor function, autoimmunity, and pathogenesis of dilated cardiomyopathy. Trends Cardiovasc. Med. 16 (2006) 20-24
21. Pearce S.H., and Leech N.J. Toward precise forecasting of autoimmune endocrinopathy. J. Clin. Endocrinol. Metab. 89 (2004) 544-547
22. Freedman N.J., and Lefkowitz R.J. Anti-beta(1)-adrenergic receptor antibodies and heart failure: causation, not just correlation. J. Clin. Invest. 113 (2004) 1379-1382
23. Forges T., Monnier-Barbarino P., Faure G.C., and Bene M.C. Autoimmunity and antigenic targets in ovarian pathology. Hum. Reprod. Updat. 10 (2004) 163-175
24. Hoebeke J. Molecular mechanisms of anti-G-protein-coupled receptor autoantibodies. Autoimmunity 34 (2001) 161-164
25. Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E., Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C., Bergmann J.E., and Gaitanaris G.A. The G protein-coupled receptor repertoires of human and mouse. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 4903-4908
26. Drysdale C.M., McGraw D.W., Stack C.B., Stephens J.C., Judson R.S., Nandabalan K., Arnold K., Ruano G., and Liggett S.B. Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 10483-10488
27. Israel E., Chinchilli V.M., Ford J.G., Boushey H.A., Cherniack R., Craig T.J., Deykin A., Fagan J.K., Fahy J.V., Fish J., Kraft M., Kunselman S.J., Lazarus S.C., Lemanske Jr. R.F., Liggett S.B., Martin R.J., Mitra N., Peters S.P., Silverman E., Sorkness C.A., Szefler S.J., Wechsler M.E., Weiss S.T., and Drazen J.M. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 364 (2004) 1505-1512
28. Wechsler M.E., Lehman E., Lazarus S.C., Lemanske Jr. R.F., Boushey H.A., Deykin A., Fahy J.V., Sorkness C.A., Chinchilli V.M., Craig T.J., DiMango E., Kraft M., Leone F., Martin R.J., Peters S.P., Szefler S.J., Liu W., and Israel E. Beta-Adrenergic receptor polymorphisms and response to salmeterol. Am. J. Respir. Crit. Care Med. 173 (2006) 519-526
29. Tattersfield A.E., and Harrison T.W. Beta-adrenoceptor polymorphisms: focus moves to long-acting beta-agonists. Am. J. Respir. Crit. Care Med. 173 (2006) 473-474
30. Hall I.P., Blakey J.D., Al Balushi K.A., Wheatley A., Sayers I., Pembrey M.E., Ring S.M., McArdle W.L., and Strachan D.P. Beta2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort: a genetic association study. Lancet 368 (2006) 771-779
31. Reinscheid R.K., Xu Y.L., Okamura N., Zeng J., Chung S., Pai R., Wang Z., and Civelli O. Pharmacological characterization of human and murine neuropeptide s receptor variants. J. Pharmacol. Exp. Ther. 315 (2005) 1338-1345
32. Melen E., Bruce S., Doekes G., Kabesch M., Laitinen T., Lauener R., Lindgren C.M., Riedler J., Scheynius A., van Hage-Hamsten M., Kere J., Pershagen G., Wickman M., and Nyberg F. Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma. Am. J. Respir. Crit. Care Med. 171 (2005) 1089-1095
33. Galvani A.P., and Novembre J. The evolutionary history of the CCR5-Delta32 HIV-resistance mutation. Microbes Infect. 7 (2005) 302-309
34. McDermott D.H., Zimmerman P.A., Guignard F., Kleeberger C.A., Leitman S.F., and Murphy P.M. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 352 (1998) 866-870
35. Zheng Z.M. Regulation of alternative RNA splicing by exon definition and exon sequences in viral and mammalian gene expression. J. Biomed. Sci. 11 (2004) 278-294
36. Park P.S., Filipek S., Wells J.W., and Palczewski K. Oligomerization of G protein-coupled receptors: past, present, and future. Biochemistry 43 (2004) 15643-15656
37. International HapMap Consortium. A haplotype map of the human genome. Nature 437 (2005) 1299-1320
38. Montpetit A., Nelis M., Laflamme P., Magi R., Ke X., Remm M., Cardon L., Hudson T.J., and Metspalu A. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population. PLoS Genet. 2 (2006) e27
39. Barnett A.H., Bain S.C., Bouter P., Karlberg B., Madsbad S., Jervell J., and Mustonen J. Angiotensin-receptor-blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N. Engl. J. Med. 351 (2004) 1952-1961
40. McConnell J.D., Roehrborn C.G., Bautista O., Andriole G.L., Dixon C.M., Kusek J.W., Lepor H., McVary K.T., Nyberg L.M., Clarke H.S., Crawford E.D., Diokno A.C., Foley J.P., Foster H.E., Jacobs S.C., Kaplan S.A., Kreder K.J., Lieber M.M., Lucia M.S., Miller G.J., Menon M., Milam D.F., Ramsdell J.W., Schenkman N.S., Slawin K.M., and Smith J.A. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N. Engl. J. Med. 349 (2003) 2387-2398
41. Squire I.B., and Barnett D.B. The rational use of beta-adrenoceptor blockers in the treatment of heart failure. The changing face of an old therapy. Br. J. Clin. Pharmacol. 49 (2000) 1-9
42. Ram F.S.F., and Sestini P. Regular inhaled short acting beta 2 agonists for the management of stable chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. Thorax 58 (2003) 580-584
43. Seeman P., and Niznik H.B. Dopamine receptors and transporters in Parkinson's diasease and schizophrenia. FASEB J. 4 (1990) 2737-2744
44. Sato S., Ohtake A., Matsushima H., Saitoh C., Usuda S., and Miyata K. Pharmacological effect of tamsulosin in relation to dog plasma and tissue concentrations: prostatic and urethral retention possibly contributes to uroselectivity of tamsulosin. J. Pharmacol. Exp. Ther.s 296 (2001) 697-703
45. Hague C., Lee S.E., Chen Z., Prinster S.C., Hall R.A., and Minneman K.P. Heterodimers of alpha1B- and alpha1D-adrenergic receptors form a single functional entity. Mol. Pharmacol. 69 (2006) 45-55
46. Ramsay D., Carr I.C., Pediani J., Lopez-Gimenez J.F., Thurlow R., Fidock M., and Milligan G. High-affinity interactions between human alpha1A-adrenoceptor C-terminal splice variants produce homo- and heterodimers but do not generate the alpha 1L-adrenoceptor. Mol. Pharmacol. 66 (2004) 228-239
47. Zanger U.M., Raimundo S., and Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn-Schmiedeberg's Arch. Pharmacol. 369 (2004) 23-37
48. Gerloff T. Impact of genetic polymorphisms in transmembrane carrier-systems on drug and xenobiotic distribution. Naunyn-Schmiedeberg's Arch. Pharmacol. 369 (2004) 69-77
49. Keffel S., Alexandrov A., Goepel M., and Michel M.C. Alpha1-Adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells. Biochem. Biophys. Res. Commun. 272 (2000) 906-911
50. Alexandrov A., Keffel S., Goepel M., and Michel M.C. Stimulation of alpha1A-adrenoceptors in Rat-1 cells inhibits extracellular signal-regulated kinase by activating p38 mitogen-activated protein kinase. Mol. Pharmacol. 54 (1998) 755-760
51. Hahntow I.N., Koopmans R.P., and Michel M.C. The beta2-adrenoceptor gene and hypertension: is it the promoter or the coding region or neither?. J. Hypertens. 24 (2006) 1003-1007
52. Pauwels P.J., Rauly I., and Wurch T. Dissimilar pharmacological responses by a new series of imidazoline derivatives at precoupled and ligand-activated alpha2A-adrenoceptor states: evidence for effector pathway-dependent differential antagonism. J. Pharmacol. Exp. Ther.s 305 (2003) 1015-1023
53. Isogaya M., Nagao T., and Kurose H. Enhanced cAMP response of naturally occurring mutant of human beta3-adrenergic receptor. Jpn. J. Pharmacol. 88 (2002) 314-318
54. Hoffstedt J., Poirier O., Thörne A., Lönnqvist F., Herrmann S.M., Cambien F., and Arner P. Polymorphism of the human beta3-adrenoceptor gene forms a well-conserved haplotype that is associated with moderate obesity and altered receptor function. Diabetes 48 (1999) 203-205
55. Candelore M.R., Deng L., Tota L.M., Kelly L.J., Cascieri M.A., and Strader C.D. Pharmacological characterization of a recently described human beta3-adrenergic receptor mutant. Endocrinology 137 (1996) 2638-2641
56. Brodde O.E., and Leineweber K. Beta2-adrenoceptor gene polymorphisms. Pharmacogenet Genomics 15 (2005) 267-275
57. Kurland L., Melhus H., Karlsson J., Kahan T., Malmqvist K., Öhman P., Nyström F., Högg A., and Lind L. Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. J. Hypertens. 20 (2002) 657-663
58. Miller J.A., Thai K., and Scholey J.W. Angiotensin II type 1 receptor gene polymorphism predicts response to losartan and angiotensin II. Kidney Int. 56 (1999) 2173-2180
59. Benetos A., Cambien F., Gautier S., Ricard S., Safar M., Laurent S., Lacolley P., Poirier O., Topouchian J., and Asmar R. Influence of the angiotensin II type 1 receptor gene polymorphism on the effect of perindopril and nitrendipine on arterial stiffness in hypertensive individuals. Hypertension 28 (1996) 1081-1084
60. Liljedahl U., Kahan T., Malmqvist K., Melhus H., Syvänen A.C., Lind L., and Kurland L. Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment. J. Hypertens. 22 (2004) 2321-2328
61. Kurland L., Melhus H., Karlsson J., Kahan T., Malmqvist K., Öhman K.P., Nyström F., Hägg A., and Lind L. Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients. J. Hypertens. 19 (2001) 1783-1787
62. Hingorani A.D., Jia H., Stevens P.A., Hopper R., Dickerson J.E., and Brown M.J. Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition. J. Hypertens. 13 (1995) 1602-1609
63. Coto E., Marin R., Alvarez V., Praga M., Fernandez Andrade C., Arias M., Poveda R., Valles M., Galceran J.M., Luno J., Rivera F., and Campistol J.M. Pharmacogenetics of angiotensin system in non diabetic nephropathy. Nefrologia 25 (2005) 381-386
64. Small K.M., McGraw D.W., and Liggett S.B. Pharmacology and physiology of human adrenergic receptor polymorphisms. Annu. Rev. Pharmacol. Toxicol. 43 (2003) 381-411
65. Lei B., Morris D.P., Smith M.P., Svetkey L.P., Newman M.F., Rotter J.I., Buchanan T.A., Beckstrom-Sternberg S.M., Green E.D., and Schwinn D.A. Novel human alpha1a-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function. Naunyn-Schmiedeberg's Arch. Pharmacol. 371 (2005) 229-239
66. Mochtar C.A., Laan W., van Houwelingen K.P., Franke B., de la Rosette J.J.M.C.H., Schalken J.A., and Kiemeney L.A.L.M. Polymorphisms in the alpha1A-adrenoceptor gene do not modify the short- and long-term efficacy of alpha 1-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia. BJU International 97 (2006) 852-855
67. Schwartz S.G., Puckett B.J., Allen R.C., Castillo I.G., and Leffler C.T. Beta1-Adrenergic receptor polymorphism and clinical efficacy of betaxolol hydrochloride in normal volunteers. Ophthalmology 112 (2005) 2131-2136
68. Sofowora G.G., Dishy V., Muszkat M., Xie H.G., Kim R.B., Harris P.A., Prasad H.C., Byrne D.W., Nair U.B., Wood A.J., and Stein C.M. A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade. Clin. Pharmacol. Ther. 73 (2003) 366-371
69. Liu J., Liu Z.Q., Tan Z.R., Chen X.P., Wang L.S., Zhou G., and Zhou H.H. Gly389Arg polymorphism of beta1-adrenergic receptor is associated with the carviovascular response to metoprolol. Clin. Pharmacol. Ther. 74 (2003) 372-379
70. Johnson J.A., Zineh I., Puckett B.J., McGorray S.P., Yarandi H.N., and Pauly D.F. Beta-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin. Pharmacol. Ther. 74 (2003) 44-52
71. S.B. Liggett, J. Mialet-Perez, S. Thaneemit-Chen, S.A. Weber, S.M. Greene, D. Hodne, B. Nelson, J. Morrison, M.J. Domanski, L.E. Wagoner, W.T. Abraham, J.L. Anderson, J.F. Carlquist, H.J. Krause-Steinrauf, L.C. Lazzeroni, J.D. Port, P.W. Lavori and M.R. Bristow, A polymorphism within a conserved beta 1-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure, Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 11288-11293.
72. Leineweber K., Büscher R., Bruck H., and Brodde O.E. Beta-adrenoceptor polymorphisms. Naunyn-Schmiedeberg's Arch. Pharmacol. 369 (2004) 1-22
73. Magnusson Y., Levin M.C., Eggertsen R., Nyström E., Mobini R., Schaufelberger M., and Andersson B. Ser49Gly of beta1-adrenergic receptor is associated with effective β-blocker dose in dilated cardiomyopathy. Clin. Pharmacol. Ther. 78 (2005) 221-231
74. Rana B.K., Insel P.A., Payne S., Abel K., Beutler E., Ziegler M.G., Schork N.J., and O'Connor D.T. A large population-based sample reveals the contribution of gene-transfer interactions in blood pressure. Hypertension (2006) (in press)
75. Scharfetter J. Pharmacogenetics of dopamine receptors and response to antipsychotic drugs in schizophrenia-An update. Pharmacogenomics 5 (2004) 691-698
76. Malhotra A.K., Murphy Jr. G.M., and Kennedy J.L. Pharmacogenetics of psychotropic drug response. Am. J. Psychiatry 161 (2004) 780-796
77. Mancama D., Arranz M.J., and Kerwin R.W. Genetic predictors of therapeutic response to clozapine. Current status of research. CNS Drugs 16 (2002) 317-324
78. Lencz T., Robinson D.G., Xu K., Ekholm J., Sevy S., Gunduz-Bruce H., Woerner M.G., Kane J.M., Goldman D., and Malhotra A.K. DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am. J. Psychiatry 163 (2006) 529-531
79. Young R., Lawford B.R., Barnes M., Burton S.C., Ritchie T., Ward W.K., and Noble E.P. Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele. Br. J. Psych. 185 (2004) 147-151
80. Lane H.Y., Hsu S.K., Liu Y.C., Chang Y.C., Huang C.h., and Chang W.H. Dopamine D 3 receptor Ser9Gly polymorphism and risperidone response. J. Clin. Psychopharmacol. 25 (2005) 6-11
81. Reynolds G.P., Templeman L.A., and Zhang Z.J. The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. Progr. Neuropsychopharmacol. Biol. Psychiatry 29 (2005) 1021-1028
82. Serretti A., and Artioli P. From molecular biology to pharmacogenetics: a review of the literature on antidepressant treatment and suggestions of possible candidate genes. Psychopharmacology 174 (2004) 490-503
83. Ellingrod V.L., Perry P.J., Ringold J.C., Lund B.C., Bever-Stille K., Fleming F., Holman T.L., and Miller D. Weight gain associated with the-759C/T polymorphism of the 5HT2C receptor and olanzapine. Am. J. Med. Genet. 134B (2005) 76-78
84. Civelli O. GPCR deorphanizations: the novel, the known and the unexpected transmitters. Trends Pharmacol. Sci. 26 (2005) 15-19
85. Thomsen W., Leonard J., and Behan D.P. Orphan GPCR target validation. Curr. Opin. Mol. Ther. 6 (2004) 640-656
86. Tang C.M., and Insel P.A. GPCR expression in the heart; "new" receptors in myocytes and fibroblasts. Trends Cardiovasc. Med. 14 (2004) 94-99
87. Hebert S.C. Therapeutic use of calcimimetics. Annu. Rev. Med. 57 (2006) 349-364
88. Sohocki M.M., Daiger S.P., Bowne S.J., Rodriquez J.A., Northrup H., Heckenlively J.R., Birch D.G., Mintz-Hittner H., Ruiz R.S., Lewis R.A., Saperstein D.A., and Sullivan L.S. Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum. Mutat. 17 (2001) 42-51
89. Teng Y., Wang W., Tian H., Wang H., Hu X., Chen Y., and Bittles A.H. Autosomal dominant retinitis pigmentosa in a five-generation pedigree in People's Republic of China. Eye 17 (2003) 1036-1039
90. Mittelman S.D., Hendy G.N., Fefferman R.A., Canaff L., Mosesova I., Cole D.E., Burkett L., and Geffner M.E. A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone. J. Clin. Endocrinol. Metab. 91 (2006) 2474-2479
91. Diaz G.A., and Gulino A.V. WHIM syndrome: a defect in CXCR4 signaling. Curr. Allergy Asthma Rep. 5 (2005) 350-355
92. Diaz G.A. CXCR4 mutations in WHIM syndrome: a misguided immune system?. Immunol. Rev. 203 (2005) 235-243
93. Puri P., and Shinkai T. Pathogenesis of Hirschsprung's disease and its variants: recent progress. Semin. Pediatr. Surg. 13 (2004) 18-24
94. Huhtaniemi I. Mutations along the pituitary-gonadal axis affecting sexual maturation: Novel information from transgenic and knockout mice. Mol. Cell. Endocrinol. 254-255 (2006) 84-90
95. Nanamori M., He R., Sang H., and Ye R.D. Normal cell surface expression and selective loss of functions resulting from Phe110 to Ser and Cys126 to Trp substitutions in the formyl peptide receptor. Immunol. Invest 33 (2004) 193-212
96. Qin M., Hayashi H., Oshima K., Tahira T., Hayashi K., and Kondo H. Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum. Mutat. 26 (2005) 104-112
97. MacDonald M.L., Goldberg Y.P., Macfarlane J., Samuels M.E., Trese M.T., and Shastry B.S. Genetic variants of frizzled-4 gene in familial exudative vitreoretinopathy and advanced retinopathy of prematurity. Clin. Genet. 67 (2005) 363-366
98. Dungan H.M., Clifton D.K., and Steiner R.A. Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion. Endocrinology 147 (2006) 1154-1158
99. Lanfranco F., Gromoll J., von Eckardstein S., Herding E.M., Nieschlag E., and Simoni M. Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism. Eur. J. Endocrinol. 153 (2005) 845-852
100. Piao X., Chang B.S., Bodell A., Woods K., Benzeev B., Topcu M., Guerrini R., Goldberg-Stern H., Sztriha L., Dobyns W.B., Barkovich A.J., and Walsh C.A. Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes. Ann. Neurol. 58 (2005) 680-687
101. Jansen A., and Andermann E. Genetics of the polymicrogyria syndromes. J. Med. Genet. 42 (2005) 369-378
102. Schulz T.F. The pleiotropic effects of Kaposi's sarcoma herpesvirus. J. Pathol. 208 (2006) 187-198
103. Geilen C.C., Husak R., and Steinhoff M. Pathogenesis and clinical manifestation of Kaposi's sarcoma. Front Radiat. Ther. Oncol. 39 (2006) 59-67
104. Bathgate R.A., Ivell R., Sanborn B.M., Sherwood O.D., and Summers R.J. International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. Pharmacol. Rev. 58 (2006) 7-31
105. Kaleva M., and Toppari J. Cryptorchidism: an indicator of testicular dysgenesis?. Cell Tissue Res. 322 (2005) 167-172
106. Bathgate R.A., Ivell R., Sanborn B.M., Sherwood O.D., and Summers R.J. Receptors for relaxin family peptides. Ann. N. Y. Acad. Sci. 1041 (2005) 61-76
107. Deprez L., Claes L.R., Claeys K.G., Audenaert D., Van Dyck T., Goossens D., Van Paesschen W., Del-Favero J., Van Broeckhoven C., and De Jonghe P. Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation. Hum. Genet. 118 (2006) 618-625
108. Weston M.D., Luijendijk M.W., Humphrey K.D., Moller C., and Kimberling W.J. Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type. Am. J. Hum. Genet. 74 (2004) 357-366
109. Robinson R., and Gardiner M. Molecular basis of Mendelian idiopathic epilepsies. Ann. Med. 36 (2004) 89-97
110. Reiners J., van Wijk E., Marker T., Zimmermann U., Jurgens K., te Brinke H., Overlack N., Roepman R., Knipper M., Kremer H., and Wolfrum U. Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Hum. Mol. Genet. 14 (2005) 3933-3943
111. MacKenzie R.G. Obesity-associated mutations in the human melanocortin-4 receptor gene. Peptides 27 (2006) 395-403
112. Govaerts C., Srinivasan S., Shapiro A., Zhang S., Picard F., Clement K., Lubrano-Berthelier C., and Vaisse C. Obesity-associated mutations in the melanocortin 4 receptor provide novel insights into its function. Peptides 26 (2005) 1909-1919
113. Palczewski K. G protein-coupled receptor rhodopsin. Annu. Rev. Biochem. 75 (2006) 743-767
114. Mendes H.F., van der Spuy J., Chapple J.P., and Cheetham M.E. Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol. Med. 11 (2005) 177-185
115. Kennan A., Aherne A., and Humphries P. Light in retinitis pigmentosa. Trends Genet. 21 (2005) 103-110
116. Bichet D.G. Nephrogenic diabetes insipidus. Adv. Chronic Kidney Dis. 13 (2006) 96-104
117. Sangkuhl K., Rompler H., Busch W., Karges B., and Schoneberg T. Nephrogenic diabetes insipidus caused by mutation of Tyr205: a key residue of V2 vasopressin receptor function. Hum. Mutat. 25 (2005) 505
118. Litonjua A.A. The significance of beta2-adrenergic receptor polymorphisms in asthma. Curr. Opin. Pulm. Med. 12 (2006) 12-17
119. Johnson J.A., and Turner S.T. Hypertension pharmacogenomics: current status and future directions. Curr. Opin. Mol. Ther. 7 (2005) 218-225
120. Sawa M., and Harada H. Recent developments in the design of orally bioavailable beta3-adrenergic receptor agonists. Curr. Med. Chem. 13 (2006) 25-37
121. Puissant B., Roubinet F., Massip P., Sandres-Saune K., Apoil P.A., Abbal M., Pasquier C., Izopet J., and Blancher A. Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts. AIDS Res. Hum. Retroviruses 22 (2006) 153-162
122. Becker Y. The molecular mechanism of human resistance to HIV-1 infection in persistently infected individuals-A review, hypothesis and implications. Virus Genes 31 (2005) 113-119
123. Bonci A., and Hopf F.W. The dopamine D2 receptor: new surprises from an old friend. Neuron. 47 (2005) 335-338
124. Sokoloff P., Diaz J., Le Foll B., Guillin O., Leriche L., Bezard E., and Gross C. The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders. CNS Neurol Disord. Drug Targets 5 (2006) 25-43
125. Gosens R., Zaagsma J., Meurs H., and Halayko A.J. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir. Res. 7 (2006) 73
126. Feng Y., Hong X., Wang L., Jiang S., Chen C., Wang B., Yang J., Fang Z., Zang T., Xu X., and Xu X. G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population. J. Allergy Clin. Immunol. 117 (2006) 612-617
127. Murugappa S., and Kunapuli S.P. The role of ADP receptors in platelet function. Front. Biosci. 11 (2006) 1977-1986
128. Johnson J.A., and Lima J.J. Drug receptor/effector polymorphisms and pharmacogenetics: current status and challenges. Pharmacogenetics 13 (2003) 525-534