Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polymerase chain reaction was used to isolate novel GTP-binding protein (G protein)-coupled receptors from bovine locus coeruleus (LC), a brain region enriched in the neuropeptide Y (NPY) system, using degenerate primers derived from the third and sixth transmembrane domains of known G protein-coupled receptors. Partial sequence analysis revealed that the polymerase chain reaction cDNA fragments were homologous to other G protein-coupled receptors. One of these cDNA fragments was used to isolate a full length cDNA clone, referred to as LCR1, from an LC cDNA library. LCR1 is 1.7 kilobases in length and encodes a predicted protein of 353 amino acids, with a membrane topology similar to that of other G protein-coupled receptors. Expression of LCR1 in mammalian cells revealed saturable and specific high affinity binding for 125I-NPY but not for any of the other ligands tested. Northern blot analysis revealed that labeled LCR1 DNA hybridized with a predominate mRNA transcript of approximately 1.7 kilobases, which was found to be most abundant in LC, cerebellum, and pons, intermediate in dorsal raphe, substantia nigra, and thalamus, and lowest in cerebral cortex and neostriatum. Significant levels of LCR1 mRNA were also present in heart, kidney, lung, and liver. This cDNA clone will be useful for studies of the regulation and function of NPY receptors, as well as for the isolation of related NPY receptor subtypes.
Mol Pharmacol 1991 Dec
PMID:Sequence and expression of a neuropeptide Y receptor cDNA. 166 37

By means of double immunolabeling procedures it has been possible to demonstrate glucocorticoid receptor (GR) immunoreactivity (IR) in large numbers of various peptidergic neurons of the brain including neurons containing gastrointestinal peptides, opioid peptides, and peptides with a hypothalamic hormone function. For each peptide system, however, marked heterogeneities exist among brain regions. Thus, in the neocortex and the hippocampal formation most of the brain peptide neurons lack GR IR, while the same types of peptide neurons in the arcuate and paraventricular nucleus [e.g. neuropeptide Y (NPY), somatostatin (SRIF) and the cholecystokinin (CCK) neurons] possess strong GR IR. Furthermore, in the arcuate, parvocellular part of the paraventricular nuclei and the central amygdaloid nucleus practically all the peptidergic neurons are strongly GR IR, while in the lateral hypothalamus, mainly the neurotensin (NT) and galanin (GAL) IR neurons are GR IR. These marked differences among areas probably reflect functional differences dependent upon their participation in stress regulated circuits. All the paraventricular NT, corticotropin-releasing factor (CRF), growth hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) and SRIF IR neurons appear to contain GR IR, while the luteinizing hormone-releasing hormone (LHRH) IR neurons lack GR IR, underlying the importance of glucocorticoids (GC) in controlling endocrine function. Finally, the GC may influence pain and mood control mainly via effects on enkephalin (ENK) neurons especially in the basal ganglia (mood) and on all beta-endorphin (beta-END) neurons of the arcuate nucleus, while most of the dynorphin neurons are not directly controlled by GC.
J Steroid Biochem Mol Biol 1991
PMID:Central peptidergic neurons as targets for glucocorticoid action. Evidence for the presence of glucocorticoid receptor immunoreactivity in various types of classes of peptidergic neurons. 168 65

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.
Brain Res Mol Brain Res 1991 Oct
PMID:Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation. 168 30

A rat medullary thyroid carcinoma cell line, CA77, was used to study the effect of a series of biosynthesized protease inhibitors on the proteolytic cleavage of the endogenously synthesized pro-CGRP. This cell line efficiently converted the pro-CGRP to mature CGRP as assessed by chromatography of cell extracts followed by radioimmunoassay for CGRP. CA77 cells were transfected with expression vectors encoding protease inhibitors: the Arg-serpins, alpha 1-antitrypsin Pittsburgh (358 Met----Arg) and plasminogen activator inhibitor 1, the Kazal type serine protease inhibitor, pancreatic secretory trypsin inhibitor, and the general thiol protease inhibitor, cystatin C. Only the chromatography of cell extracts from CA77 cells transfected with a plasmid encoding cystatin C showed an apparent higher content of unprocessed pro-CGRP as compared to non-transfected cells. No effect on pro-CGRP processing could be measured in the CA77 cells transfected with plasmids encoding the three serine protease inhibitors. CA77 cells were also transfected with two constructs encoding chimeric proteins consisting of cystatin C and the precursor for neuropeptide Y. Release experiments using 8-bromo cAMP as the secretagogue showed that the chimer was co-released with CGRP. However, no effect of this chimer upon pro-CGRP processing could be detected. It is concluded that the processing of pro-CGRP in the CA77 cell line was very efficient and that four different protease inhibitors and two cystatin C/NPY chimers synthesized by this neuroendocrine cell line had only minimal effect upon the processing of CGRP.
Mol Cell Endocrinol 1991 Nov
PMID:Processing of pro-CGRP in a rat medullary thyroid carcinoma cell line transfected with protease inhibitors. 176 Nov 66

We have developed a rapid and simple method for quantitative Northern blot analysis of rare messenger RNA species from single mouse hypothalami and adrenals. This technique has allowed us to study the effects of food deprivation on neuropeptide gene expression in the mouse hypothalamus and adrenal gland. The potential modulatory effects of sex and age were also investigated. Food deprivation induced a two-fold increase in the amount of hypothalamic neuropeptide Y (NPY) mRNA, but did not increase NPY mRNA in the brainstem. Age had a significant effect on levels of NPY messenger RNA levels in the hypothalamus. However, there were no gender-associated effects. Sexually immature females (6 weeks old) had higher levels of NPY expression than mature females (9 weeks old). In contrast, in the adrenal gland, increasing maturity was associated with higher levels of NPY mRNA. As in the hypothalamus, fasting caused approximately two-fold increases in NPY mRNA over levels in the ad libitum fed state for both mature and immature mice. Thus, hypothalamic NPY neurons are responsive to nutritional deprivation and developmental status, suggesting that NPY neurons may be important in energy homeostasis.
Brain Res Mol Brain Res 1991 Jan
PMID:Food deprivation and age modulate neuropeptide gene expression in the murine hypothalamus and adrenal gland. 185 82

With an assay based on the radioimmunological detection of the formation of the C-terminal amide function on a neuropeptide Y-like substrate, amidation enzyme activity with apparent Mr of 56,000 and 38,000 was found in pheochromocytoma extracts. The larger molecular form of amidating enzyme was also expressed and secreted from medullary thyroid carcinoma cells in a dexamethasone-suppressible way. Serum contained high levels of amidating enzyme activity with no difference between normal subjects and patients with pheochromocytomas. However, the majority of the amidating activity in serum was of much larger size, Mr between 80 and 105,000, compared to that released from the endocrine cells. No major difference was found between the molecular forms of amidation enzyme from tissues and from serum either in respect of enzyme kinetics or in respect of requirements for the cofactors copper and ascorbate. The major serum forms of enzyme were relatively independent of exogenous copper; however, they could still be quenched by cobber chelating agents. It is concluded that the molecular weight forms of the amidating enzyme circulating in serum are much larger than the soluble enzyme stored and secreted from most endocrine tissues.
Mol Cell Endocrinol 1991 Aug
PMID:Comparison of peptidyl-glycine alpha-amidation activity in medullary thyroid carcinoma cells, pheochromocytomas, and serum. 193 46

1. Specific binding sites for neuropeptide Y (NPY) and peptide YY (PYY) were investigated in rat brain areas using quantitative receptor autoradiography with 125I-Bolton-Hunter NPY (125I-BH-NPY) and 125I-PYY, radioligands for PP-fold family peptides receptors. 2. There were no differences between localization of 125I-BH-NPY and 125I-PYY binding sites in the rat brain. High densities of the binding sites were present in the anterior olfactory nucleus, lateral septal nucleus, stratum radiatum of the hippocampus, posteromedial cortical amygdaloid nucleus, and area postrema. 3. In cold ligand-saturation experiments done in the presence of increasing concentrations of unlabeled NPY and PYY, 125I-BH-NPY and 125I-PYY binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, molecular layer of the cerebellum, and area postrema was single and of a high affinity. There was a significant difference between the affinities of 125I-BH-NPY (Kd = 0.96 nM) and 125I-PYY binding (Kd = 0.05 nM) to the molecular layer of the cerebellum. The binding of the two radioligands to the other areas examined had the same affinities. 4. When comparing the potency of unlabeled rat pancreatic polypeptide (rPP), a family peptide of NPY and PYY, to inhibit the binding to the areas examined, rPP displaced 125I-BH-NPY and 125I-PYY binding to the area postrema more potently than it did the binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, and molecular layer of the cerebellum. 5. Thus, the quantitative receptor autoradiographic method with 125I-BH-NPY and 125I-PYY revealed differences in binding characteristics of specific NPY and PYY binding sites in different areas of the rat brain. The results provide further evidence for the existence of multiple NPY-PYY receptors in the central nervous system.
Cell Mol Neurobiol 1990 Dec
PMID:Neuropeptide Y (NPY) and peptide YY (PYY) receptors in rat brain. 196 25

The gene encoding for pre-prosomatostatin is located on chromosome 16 of the mouse. To determine the effect of an extra copy of this gene on somatostatin expression in neurons, primary disaggregated cultures of neocortex prepared from 15 days gestational Trisomy 16 mice and their littermate euploid controls were subjected to immunocytochemical staining for somatostatin, neuropeptide Y and glutamic acid decarboxylase. The results demonstrate a selective and significant increase in the number of somatostatin-immunoreactive neurons.
Brain Res Mol Brain Res 1990 Apr
PMID:Increased number of somatostatin-immunoreactive neurons in primary cultures of trisomy 16 mouse neocortex. 197 Aug 46

A series of fragments and analogues of neuropeptide Y (NPY), both human (hNPY) and porcine (pNPY), were synthesized and tested for their affinities at brain NPY receptor binding sites and their potencies in inhibiting the electrically stimulated twitch response of rat vas deferens. Results with N- and C-terminal fragments suggest that amino acid residues in the N-terminal portion of the molecule are mostly important for recognition of brain and vas deferens NPY receptors, in addition to being relevant for the maintenance of adequate receptor affinity. On the other hand, C-terminal amino acid residues appear to be responsible for triggering receptor activation in the rat vas deferens preparation, because full intrinsic activity is maintained with fragments up to NPY18-36. C-terminal fragment NPY25-36 and N-terminal fragment NPY1-15 were devoid of affinity for [3H]NPY brain receptor sites and showed no activity in the rat vas deferens preparation. Similarly, N-terminal fragment hNPY1-24CONH2 showed no affinity toward [3H]NPY brain receptor sites and no inhibition of the twitch response in the rat vas deferens preparation at concentrations up to 1.0 microM. On the contrary, this fragment appears to selectively increase the amplitude of the twitch response to electrical stimulation at low micromolar concentrations, an effect opposite to that of NPY and all other NPY fragments and analogues studied here. The exact mechanism mediating this contractile action of hNPY1-24CONH2 remains to be established. Modifications of the tyrosine residue in position 20 led to the development of two analogues, [D-Tyr20]hNPY and [D-Trp20]hNPY, which show an apparent preference for the vas deferens NPY receptor. On the other hand, substitutions of the tyrosine residue in position 21 by a phenylalanine ([Phe21]hNPY) or a methylated tyrosine residue ([Tyr-O-Me21]hNPY) produced analogues demonstrating an apparent preference for the brain receptor site. This suggests that modifications of tyrosine residues at positions 20 and/or 21 may eventually lead to the development of NPY analogues distinguishing between the most abundant class of sites present in the brain and vas deferens, respectively.
Mol Pharmacol 1990 Oct
PMID:Comparative structural requirements of brain neuropeptide Y binding sites and vas deferens neuropeptide Y receptors. 217 66

To elucidate how the neuropeptide Y (NPY) gene is regulated by physiological/pharmacological changes in neural functions, the expression and regulation of the NPY gene were studied by measuring changes in the abundances of NPY and NPY mRNA in the adrenal gland and brain regions of rats in vivo and in PC12 rat pheochromocytoma cells after reserpine treatment. Long term treatment with reserpine in vivo, which causes hypotension and increased splanchnic nerve activity, induced prolonged increases in the abundance of NPY mRNA and putative NPY pre-mRNA, with concomitant increases in NPY, in the adrenal gland in a tissue-dependent manner but caused no changes in the abundance of beta-actin mRNA. Transection of the splanchnic nerves almost completely (76%) prevented the reserpine-induced increases in the abundance of NPY mRNA and NPY pre-mRNA, but denervation alone did not affect their steady state levels. These results suggested that increased activity of the splanchnic nerves regulates NPY gene expression positively in the adrenal gland, probably at the level of transcription. In PC12 cells, reserpine decreased the abundance of NPY mRNA directly, but nicotinic receptor activation increased its abundance transiently and the persistent membrane depolarization increased its abundance markedly. Thus, NPY gene expression is positively regulated by membrane depolarization via increased transsynaptic activation with reserpine.
Mol Pharmacol 1990 Nov
PMID:Long lasting increase in neuropeptide Y gene expression in rat adrenal gland with reserpine treatment: positive regulation of transsynaptic activation and membrane depolarization. 223 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>