Structure of the Human Melanin Concentrating Hormone mRNA

Presse, Françoise; Nahon, Jean‐Louis; Fischer, Wolfgang; Vale, Wylie

doi:10.1210/mend-4-4-632

Cited by 106 publications

(52 citation statements)

References 19 publications

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“…The rat hypothalamic MCH is a 19-aminoacid cyclic peptide that differs from the salmon MCH in that it has an N-terminal extension of two amino acids and two other substitutions (Vaughan , 1989). MCH is derived from post-translational cleavage of the C-terminal of a larger precursor molecule consisting of 165 amino acids called pre-proMCH (Presse et al, 1990). …”

Section: Introductionmentioning

confidence: 99%

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

et al. 2007

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The presence of melanin-concentrating hormone (MCH) containing processes, projecting from the lateral hypothalamus to the medial nucleus tractus solitarius (mNTS), has been reported in the rat. It was hypothesized that MCH acting within the mNTS may modulate the central regulation of cardiovascular function. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of MCH (0.25, 0.5, 0.75, and 1 mM) into the mNTS of anesthetized rats elicited decreases in mean arterial pressure (20.4 ± 1.6, 50.7 ± 3.3, 35.7 ± 2.8 and 30.0 ± 2.6 mmHg, respectively). The decreases in heart rate in response to these concentrations of MCH were 40.0 ± 8.7, 90.0 ± 13.0, 48.0 ± 7.3 and 48.0 ± 8.0 beats/min, respectively. Maximum cardiovascular responses were elicited by a 0.5 mM concentration of MCH. Cardiovascular responses to MCH were similar in unanesthetized mid-collicular decerebrate rats. Control microinjections of normal saline (100 nl) did not elicit any cardiovascular response. Ipsilateral or bilateral vagotomy significantly attenuated MCH-induced bradycardia. Prior microinjections of PMC-3881-PI (2 mM; MCH-1 receptor antagonist) into the mNTS blocked the cardiovascular responses to microinjections of MCH. Microinjection of MCH (0.5 mM) into the mNTS decreased efferent greater splanchnic nerve activity. Direct application of MCH (0.5 mM; 4 nl) to barosensitive NTS neurons increased their firing rate. These results indicate that: 1) MCH microinjections into the mNTS activate MCH-1 receptors and excite barosensitive NTS neurons, causing a decrease in efferent sympathetic activity and blood pressure, and 2) MCH-induced bradycardia is mediated via the activation of the vagus nerves.

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Section: Introductionmentioning

confidence: 99%

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

et al. 2007

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“…Our previous structure-function studies on hMCH yielded a cyclic peptide consisting of the disulfide ring and Arg 6 of hMCH: the so-called "active core" of hMCH with the four residues, Arg 6 , Met 8 , Arg 11 , and Tyr 13 , critical for molecular recognition at hMCH-1R and hMCH-2R (24 -27). This compound, Ac-hMCH(6 -16)-NH 2 (Structure 2), was equipotent to the fulllength hMCH at both receptors.…”

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confidence: 99%

Synthesis and Biological Evaluation in Vitro of a Selective, High Potency Peptide Agonist of Human Melanin-concentrating Hormone Action at Human Melanin-concentrating Hormone Receptor 1

Bednarek

Tan

Hreniuk

et al. 2002

Journal of Biological Chemistry

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Human melanin-concentrating hormone (hMCH) is a nonselective natural ligand for the human melanin-concentrating hormone receptors: hMCH-1R and hMCH-2R. Similarly, the smaller peptide encompassing the disulfide ring and 50 ‫؍‬ 47 nM) with more than 200-fold selectivity with respect to hMCH-2R. Apparently, these structural changes in positions 6 and 10 results in peptide conformations that allow for efficient interactions with hMCH-1R but are unfavorable for molecular recognition at hMCH-2R.In the last couple of years, melanin-concentrating hormone (MCH) 1 emerged as an important regulator of feeding behavior in rodents (1-7). Similarly to neuropeptide Y, this hormone stimulates appetite in rats when injected intracerebroventricularly, and this orexigenic effect is inhibited by anorectic peptides such as ␣-melanocyte stimulating hormone, glucagon-like peptide 1, and neurotensin (1-7). Additionally, in the hypothalamus of genetically obese (ob/ob) and fasting mice, the level of MCH messenger RNA is elevated, and the metabolic rate of mice lacking MCH is increased. MCH (see Structure 1 for human/rat MCH) also appears to be involved in other biological functions such as regulation of the hypothalamic-pituitarythyroid axis. In humans, this 19-amino acid cyclic peptide is found in the brain, in the lateral hypothalamus and the zona incerta, and acts through specific receptors (8 -12). At present, two receptors are known with which hMCH interacts: hMCH-1R and hMCH-2R (13-23). These receptors are members of the family of G-protein-coupled receptors and their activation leads to mobilization of intracellular calcium. Binding of hMCH to hMCH-1R results in reduction of forskolin-elevated cyclic AMP levels, but binding to hMCH-2R does not cause this effect. The physiological role of hMCH-2R is less well understood than the physiological role of hMCH-1R, but the presence of the MCH-2R messenger RNA in the brain regions implicated in the regulation of body weight suggests that this receptor might also be involved in the regulation of feeding behavior (19 -23).To understand and separate the physiological functions of the MCH receptors, selective agonists are required, because hMCH is a nonspecific natural ligand for both hMCH-1R and hMCH-2R. Similarly, the synthetic ligands reported in the literature do not distinguish between the receptors (13-23).Our previous structure-function studies on hMCH yielded a cyclic peptide consisting of the disulfide ring and Arg 6 of hMCH: the so-called "active core" of hMCH with the four residues, Arg 6 , Met 8 , Arg 11 , and Tyr 13 , critical for molecular recognition at hMCH-1R and hMCH-2R (24 -27). This compound, Ac-hMCH(6 -16)-NH 2 (Structure 2), was equipotent to the fulllength hMCH at both receptors. Moreover, at hMCH-1R, an analog of Ac-hMCH(6 -16)-NH 2 with D-Arg in position 6 was as potent as the parent compound, but, at hMCH-2R, this analog was a noticeably weaker agonist. The D-Arg 6 compound was the first described peptide agonist with enhanced hMCH-1R selectivity with respect to ...

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“…3). This putative phosphorylation site is absent in mammalian MCH precursors (19,29). Similarly a tyrosine phosphorylation site can be predicted at Tyr126 close to Arg124 (Fig.…”

Section: Discussionmentioning

confidence: 55%

Identification of a Single Melanin‐Concentrating Hormone Messenger Ribonucleic Acid in Coho Salmon: Structural Relatedness with 7SL Ribonucleic Acid

Nahon

Presset

Schoepfer

et al. 1991

J Neuroendocrinology

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Melanin-concentrating hormone (MCH) is a cyclic neuropeptide possessing antagonistic function to a-melanocyte-stimulating hormone and corticotropin-releasing factor in the control of melanosome dispersion within melanophores and adrenocorticotropin release in fish. We have isolated and characterized MCH cDNAs from coho salmon (Oncorhyncus kisutch). The precursor protein predicted by the longest cDNA consists of 132 amino-acids with a characteristic signal peptide at the N-terminus and the biologically active salmon MCH (sMCH) peptide at the C-terminus. The coho sMCH mRNA and protein sequences are very similar but not identical to the previously reported chum or chinook salmon counterparts, suggesting the existence of species polymorphism. Sequence similarities were revealed between a-melanocyte-stimulating hormone and part of the C-terminal domain of sMCH precursor. Two sMCH genes were found in coho salmon. By contrast to other salmon species, only one major sMCH mRNA was detected in coho species suggesting that differential MCH gene expression might occur in salmon. In addition, under low stringency oligoprobes complementary to the sMCH RNA recognize a 0.3 kb RNA which was identified as the 7SL RNA. The regions conserved between those RNAs fold in a similar secondary structure. These similarities might reflect common ancestry which may have functional significance.

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Structure of the Human Melanin Concentrating Hormone mRNA

Cited by 106 publications

References 19 publications

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

Synthesis and Biological Evaluation in Vitro of a Selective, High Potency Peptide Agonist of Human Melanin-concentrating Hormone Action at Human Melanin-concentrating Hormone Receptor 1

Identification of a Single Melanin‐Concentrating Hormone Messenger Ribonucleic Acid in Coho Salmon: Structural Relatedness with 7SL Ribonucleic Acid

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