ライフサイエンスコーパス: MC3R

1 MC3R(hDM/hDM) bone- and adipose tissue-derived mesenchym

2 MC3R(hDM/hDM) impacts nutrient partitioning to generate

3 MC3R(hDM/hDM) mice do not have increased adipose tissue

4 MC3R-deficient (MC3R(-)(/)(-)) mice demonstrate increase

5 MC3Rs are expressed in hypothalamic and limbic regions o

6 ociations of C17A + G241A and +2138InsCAGACC MC3R variants with children's energy balance.

7 s, melanocortin-4 (MC4R) and melanocortin-3 (MC3R), are involved in the regulation of satiety and ene

8 ysiological effect that one MCR, MCR type 3 (MC3R), might have on vascular inflammation.

9 old was derived from results obtained from a MC3R mixture-based positional scanning campaign.

10 s blocked by a neutralizing antibody against MC3R.

11 and natural [agouti-related protein (AGRP)] MC3R antagonists but not by the MC4R antagonist Ac-Cys-N

12 Functional analysis of this altered MC3R (I183N) has indicated that the mutation completely

13 Leptin-deficient and MC3R-/- mice regulate metabolic rate similarly to wild-t

14 Two melanocortin receptors (MC1 and MC3R) have been identified as main transducers of the an

15 MC1R and MC3R mRNA and protein were both expressed in the inflame

16 at the mouse melanocortin receptors MC1R and MC3R-MC5R and human melanocytes known to express the MC1

17 We studied MC4R and MC3R mutations detected in a total of 1821 adults (889 s

18 nces of all mutations found in both MC4R and MC3R.

19 vels are increased in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects.

20 ant effect on hypothalamic POMC, orexin, and MC3R levels.

21 reopening of the superior mesenteric artery, MC3R-null mice displayed a higher degree of plasma extra

22 was used to examine the associations between MC3R polymorphisms and the measures of energy balance.

23 nce of a tonic inhibitory signal provided by MC3R in the mesenteric microcirculation of the mouse, ac

24 The impact of central MC3Rs on behavior and metabolism involves divergent path

25 To investigate the roles of central MC3Rs, we inserted a "lox-stop-lox" (LoxTB) 5' of the tr

26 MC3R-deficient (MC3R(-)(/)(-)) mice demonstrate increased fat mass, high

27 These data demonstrated MC3R deficiency caused a reduction of food intake and bo

28 useful for in vivo studies to differentiate MC3R vs MC4R physiological roles in animal models, such

29 Furthermore, the endogenous MC3R and MC4R antagonist, agouti-related protein (AgRP),

30 main confers AGRP's distinct selectivity for MC3R and MC4R.

31 rphisms in the melanocortin-3 receptor gene (MC3R) coding sequence, C17A and G241A, has been reported

32 le-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater weight and fat mas

33 the intracellular cAMP accumulation in human MC3R, MC4R, and MC5R revealed that the native peptide sh

34 is the most selective analogue for the human MC3R reported thus far.

35 however with poor selectivity for the human MC3R-MC5R.

36 /hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater wei

37 we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3

38 attributed to a limited number of identified MC3R selective ligands.

39 kine generation; such effects were absent in MC3R-null mice.

40 0), but not Arg(7), result in an increase in MC3R selectivity over the MC4R and MC5R and only agonist

41 Serum adiponectin levels are increased in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects.

42 to antagonist at MC2R, which was observed in MC3R and MC4R.

43 -MSH led to accumulation of cAMP, indicating MC3R receptor functionality: this effect was blocked by

44 cking because of the limited number of known MC3R selective ligands.

45 ng two MC5R orthologues, while Fugu, lacking MC3R, has only four.

46 e endogenous nonselective agonists for MC1R, MC3R, MC4R, and MC5R.

47 he role of Phe(7) in ACTH on human (h) MC1R, MC3R, and MC4R binding and signaling.

48 ayed for agonist activity at the mouse MC1R, MC3R, MC4R, and MC5R.

49 ty at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R.

50 ty at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R.

51 ty at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R.

52 n 2 (FABP2), melanocortin 2 receptor (MC2R), MC3R, PPARG coactivator 1 alpha (PPARGC1A), and tumor ne

53 nomolar MC1R and MC5R potency but micromolar MC3R and MC4R agonist potency.

54 dy is to determine the structural aspects of MC3R responsible for ligand binding and receptor signali

55 ever, the specific molecular determinants of MC3R responsible for ligand binding and receptor signali

56 respective roles especially the functions of MC3R need more exploration.

57 These data confirm the importance of MC3R signalling in human metabolism and suggest a previo

58 At least one specific mutation of MC3R has been identified to be associated with human obe

59 ining the complicated signalling pathways of MC3R and MC4R.

60 her variant in the 3' untranslated region of MC3R, has also been described.

61 These results suggest that actions of MC3Rs impacting on energy homeostasis involve both centr

62 mutations impairing the function of MC4R or MC3R were associated with severe obesity in North Americ

63 ectivity (223- to 467-fold) toward MC4R over MC3R and MC5R receptor subtypes without compromising ago

64 MC4R, was more than 200-fold selective over MC3R, and had a good pharmacokinetic profile in mice, in

65 The three most potent MC3R agonists, 18 [Ac-Arg-Arg-(pI)DPhe-Tic-NH2], 1 [Ac-H

66 In contrast, the prevalence of rare MC3R variants was not significantly increased in severel

67 and antagonists of melanocortin-3 receptor (MC3R) and MC4R point to the importance of the CNS melano

68 ortin (POMC) at the melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) and has been pr

69 The melanocortin-3 receptor (MC3R) gene is pleiotropic, influencing body composition,

70 ogical roles of the melanocortin-3 receptor (MC3R) is lacking because of the limited number of known

71 in homology (Pten), melanocortin-3 receptor (MC3R), and NPY-Y1R were determined.

72 lated receptor, the Melanocortin-3 receptor (MC3R), could also be a cause of severe human obesity.

73 Melanocortin-3 receptor (MC3R), primarily expressed in the hypothalamus, plays an

74 ogical roles of the melanocortin-3 receptor (MC3R).

75 ous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits pot

76 ous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits pot

77 Melanocortin-3 receptors (MC3R) have a contextual role in appetite control that is

78 Melanocortin-3 and 4 receptors (MC3R and MC4R) can regulate energy homeostasis, but thei

79 gonizes the melanocortin-3 and -4 receptors (MC3R and MC4R).

80 melanocortin-3 and melanocortin-4 receptors (MC3R, MC4R) are involved in the metabolic and food intak

81 The melanocortin-3 and -4 receptors (MC3R, MC4R) have been implicated in energy homeostasis a

82 nist of the melanocortin-3 and -4 receptors (MC3R, MC4R).

83 y expressed melanocortin-3 and -4 receptors (MC3R/MC4R) have been studied as possible targets for wei

84 Two of the five melanocortin receptors, MC3R and MC4R are involved in hypothalamic control of en

85 ogical treatment of animals with a selective MC3R agonist ([D-Trp(8)]-gamma-melanocyte-stimulating ho

86 lpha-MSH, melanotan II (MTII), and selective MC3R or MC4R agonists were all inhibitory, reducing the

87 e of the recent description of the selective MC3R agonist [d-Trp(8)]-gamma-melanocyte-stimulating hor

88 ata support the development of the selective MC3R agonist [d-Trp(8)]-gamma-MSH for the treatment of i

89 In summary, MC3Rs expressed in Nkx2.1(+ve) neurons are sufficient to

90 cytes that accumulate more triglyceride than MC3R(hWT/hWT) MSCs.

91 from identified neurons, we demonstrate that MC3R and MC4R agonists depolarize arcuate POMC neurons a

92 C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater weight and fat mass, increase

93 However, our data suggest that MC3R mutations are not associated with severe obesity in

94 tensively studied, little is known about the MC3R.

95 ght stimulatory activity was observed at the MC3R (at up to 100 microM concentration).

96 native peptide shows potent activity at the MC3R (EC(50) = 5.9 nM) and is about 50-100-fold selectiv

97 further truncation decreases potency at the MC3R and MC4R.

98 = 3 nM), which is more potent than 7 at the MC3R but not as selective.

99 1 order of magnitude (IC(50) = 6 nM) at the MC3R compared with that of the natural molecule and an i

100 and 250-fold increase in selectivity at the MC3R compared with the MC4R and MC5R, respectively.

101 10-fold more potent (IC(50) = 8.8 nM) at the MC3R compared with the native peptide but lacks subtype

102 electivity of 1-2 orders of magnitude at the MC3R over the MC4R and MC5R.

103 melanocortin neurons selectively express the MC3R, which provides a neuroanatomical basis for a dual-

104 highly selective antagonist analogue for the MC3R (560-fold vs the hMC4R and about 3000-fold vs the h

105 ly, the DTyr(1) peptide is selective for the MC3R (EC(50) = 12 nM) by 40-200-fold compared with the M

106 50) = 11 nM) analogues are selective for the MC3R by 1 and 2 orders of magnitude compared with the MC

107 ecule and an increase in selectivity for the MC3R by 2 orders of magnitude compared with the activity

108 ggest a previously-unrecognized role for the MC3R in adipose tissue development.

109 bility of ligands that are selective for the MC3R.

110 agonist selectivity for the MC4R versus the MC3R.

111 gonist ligand for the hMC5R (560-fold vs the MC3R and 1000-fold vs the MC4R); (2) compound 7, Ac-c[Cy

112 spectively, and had no detectable binding to MC3R.

113 y from ADA (the adenosine deaminase gene) to MC3R (the melanocortin 3 receptor gene).

114 viously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mas

115 he His(6) position can determine MC4R versus MC3R agonist selectivity and that chemically nonreactive

116 tified a new and novel >200-fold MC4R versus MC3R selective peptide Tyr-c[Asp-D-Phe-Arg-Trp-Asn-Ala-P

117 VMH MC3R signaling was not sufficient to rescue the lean mas

118 metabolism involves divergent pathways; VMH MC3R signaling improves metabolic homeostasis but does n

119 Although restoring VMH MC3R signaling also had a modest impact on obesity, mark

120 To target VMH MC3R expression, we used the steroidogenic factor-1 Cre

121 ment of 1, a potent, selective (1184-fold vs MC3R, 350-fold vs MC5R), small-molecule agonist of the M

122 pitous discovery of nine compounds that were MC3R agonists (EC50 < 1000 nM) and MC4R antagonists (5.7

123 duced length and fat-free mass compared with MC3R(hWT/hWT).

124 mistry and their perikarya distribution with MC3R and MC4R by double in situ hybridization.