7 results on '"Low MJ"'
Search Results
2. A tale of two carboxypeptidases.
- Author
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Low MJ
- Abstract
Proopiomelanocortin (Pomc) neurons play a central role in energy homeostasis. Despite the complexity of Pomc posttranslational processing, regulation of Pomc gene expression often takes center stage. Complementary papers that zero in on distinct carboxypeptidases (Plum et al., 2009; Wallingford et al., 2009) now refocus the spotlight on regulated peptide cleavage.
- Published
- 2009
- Full Text
- View/download PDF
3. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.
- Author
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Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, and Horvath TL
- Subjects
- Agouti-Related Protein, Animals, Central Nervous System cytology, Corticotropin-Releasing Hormone biosynthesis, Female, Ghrelin, Hypothalamus cytology, Hypothalamus drug effects, In Vitro Techniques, Intercellular Signaling Peptides and Proteins, Luminescent Proteins biosynthesis, Mice, Mice, Knockout, Mice, Transgenic, Neurons cytology, Neurons metabolism, Neuropeptide Y biosynthesis, Organ Specificity, Paraventricular Hypothalamic Nucleus drug effects, Paraventricular Hypothalamic Nucleus metabolism, Patch-Clamp Techniques, Peptide Hormones pharmacology, Presynaptic Terminals metabolism, Pro-Opiomelanocortin biosynthesis, Protein Binding physiology, Protein Biosynthesis, Rats, Central Nervous System metabolism, Energy Metabolism physiology, Homeostasis physiology, Hypothalamus metabolism, Nerve Net metabolism, Peptide Hormones metabolism, Proteins
- Abstract
The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH). Within the hypothalamus, ghrelin bound mostly on presynaptic terminals of NPY neurons. Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH). We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis.
- Published
- 2003
- Full Text
- View/download PDF
4. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides.
- Author
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Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, and Cone RD
- Subjects
- Animals, Body Temperature Regulation, Female, Genomic Library, Harderian Gland physiology, Lacrimal Apparatus physiology, Male, Mice, Mice, Knockout, Mice, Transgenic, Organ Specificity, Penis, Porphyrins metabolism, RNA, Messenger biosynthesis, Rats, Receptors, Corticotropin biosynthesis, Receptors, Melanocortin, Sebaceous Glands physiology, Transcription, Genetic, Transfection, Exocrine Glands physiology, Receptors, Corticotropin deficiency, Receptors, Corticotropin genetics
- Abstract
The effects of pituitary-derived melanocortin peptides are primarily attributed to ACTH-mediated adrenocortical glucocorticoid production. Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregulation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland. These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides.
- Published
- 1997
- Full Text
- View/download PDF
5. Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine.
- Author
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Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, and Grandy DK
- Subjects
- 3,4-Dihydroxyphenylacetic Acid metabolism, Amino Acid Sequence, Animals, Antipsychotic Agents pharmacology, Behavior, Animal drug effects, Clozapine pharmacology, Corpus Striatum anatomy & histology, Corpus Striatum chemistry, Corpus Striatum metabolism, Dopamine metabolism, Genotype, Humans, Levodopa analysis, Levodopa pharmacokinetics, Locomotion drug effects, Maternal Behavior drug effects, Mice, Mice, Knockout, Molecular Sequence Data, Motor Activity drug effects, Mutagenesis, Site-Directed physiology, Nucleus Accumbens chemistry, Nucleus Accumbens metabolism, Receptors, Dopamine D2 deficiency, Receptors, Dopamine D4, Sensitivity and Specificity, Substantia Nigra anatomy & histology, Substantia Nigra chemistry, Substantia Nigra metabolism, Transcription, Genetic genetics, Central Nervous System Depressants pharmacology, Cocaine pharmacology, Dopamine Agents pharmacology, Ethanol pharmacology, Methamphetamine pharmacology, Narcotics pharmacology, Receptors, Dopamine D2 genetics
- Abstract
The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.
- Published
- 1997
- Full Text
- View/download PDF
6. Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice.
- Author
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Kelly MA, Rubinstein M, Asa SL, Zhang G, Saez C, Bunzow JR, Allen RG, Hnasko R, Ben-Jonathan N, Grandy DK, and Low MJ
- Subjects
- Animals, Female, Male, Mice, Mice, Mutant Strains, Prolactin blood, Sex Factors, Hyperplasia metabolism, Hyperprolactinemia metabolism, Pituitary Gland metabolism, Receptors, Dopamine D2 genetics
- Abstract
Dopamine secreted from hypophysial hypothalamic neurons is a principal inhibitory regulator of pituitary hormone secretion. Mice with a disrupted D2 dopamine receptor gene had chronic hyperprolactinemia and developed anterior lobe lactotroph hyperplasia without evidence of adenomatous transformation. Unexpectedly, the mutant mice had no hyperplasia of the intermediate lobe melanotrophs. Aged female D2 receptor -/- mice developed uterine adenomyosis in response to prolonged prolactin exposure. These data reveal a critical role of hypothalamic dopamine in controlling pituitary growth and support a multistep mechanism for the induction and perpetuation of lactotroph hyperplasia, involving the lack of dopamine signaling, a low androgen/estrogen ratio, and a final autocrine or paracrine "feed-forward" stimulation of mitogenesis, probably by prolactin itself.
- Published
- 1997
- Full Text
- View/download PDF
7. Tissue-specific posttranslational processing of pre-prosomatostatin encoded by a metallothionein-somatostatin fusion gene in transgenic mice.
- Author
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Low MJ, Hammer RE, Goodman RH, Habener JF, Palmiter RD, and Brinster RL
- Subjects
- Animals, DNA, Recombinant, Female, Kidney metabolism, Liver metabolism, Male, Metallothionein genetics, Mice, Organ Specificity, Pituitary Gland, Anterior metabolism, Protein Precursors genetics, Somatostatin biosynthesis, Somatostatin blood, Somatostatin genetics, Spleen metabolism, Protein Precursors metabolism, Protein Processing, Post-Translational, Somatostatin metabolism
- Abstract
The somatostatins are neuropeptides of 14 and 28 amino acids that inhibit the release of growth hormone and other hypophyseal and gastrointestinal peptides. These neuropeptides are cleaved posttranslationally from a common precursor, pre-prosomatostatin. We report here the production and processing of pre-prosomatostatin by transgenic mice carrying a metallothionein-somatostatin fusion gene. The most active site of somatostatin production, as determined by hormone concentrations in the tissues, is the anterior pituitary, a tissue that does not normally synthesize somatostatin-like peptides. Anterior pituitary processed pre-prosomatostatin almost exclusively to the two biologically active peptides, somatostatin-14 and somatostatin-28, whereas the liver and kidney synthesized much smaller quantities of predominantly a 6000 dalton somatostatin-like peptide. The growth of the transgenic mice was normal despite high plasma levels of the somatostatin-like peptides. These studies indicate that proteases which cleave prosomatostatin to somatostatin-28 and somatostatin-14 are not specific to tissues that normally express somatostatin.
- Published
- 1985
- Full Text
- View/download PDF
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