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

The aim of this study was to determine the effect of repeated electroconvulsive stimulation (ECS) on the expression of neuropeptide Y (NPY) and somatostatin (SS) mRNA in the rat brain. For that purpose, quantitative in situ hybridization histochemistry and RNA blot analysis were used. In the hippocampal formation the prevalence of NPY mRNA positive neurons increased in the hilus of the dentate gyrus and the CA3 while a decrease was seen in layers II-III of the entorhinal cortex. In contrast, SS mRNA was increased in the granule cells of the dentate gyrus and in most neurons of the outer parts of the layer III in the entorhinal cortex with cell bodies of perforant pathway projections to the hippocampal CA1 region. Both NPY and SS mRNA expressing neurons were increased in numerical density in the prefrontal cortex with similar amounts of mRNA in individual NPY positive neurons after the stimulations while SS mRNA levels decreased in hybridization positive neurons. In the striatum the only observed significant effect was an increased prevalence of NPY mRNA positive neurons in the caudal nucleus accumbens. Our results provide an outline of a complex functional anatomy of ECS in the rat brain. This type of investigations contributes to map the neuronal systems involved in the action of ECT used in the treatment of affective and schizophrenic disorders.
Brain Res Mol Brain Res 1995 Jul
PMID:Limbic effects of repeated electroconvulsive stimulation on neuropeptide Y and somatostatin mRNA expression in the rat brain. 747 35

We are investigating the nature of the chemical interactions between the neuropeptide Y (NPY) and its cell surface receptor (Y1). A previous study involving site-directed mutagenesis and computer-aided modelling (Walker et al., 1994) suggested that the C-terminal Tyr36 of NPY, known to be a key residue for receptor binding, might dock at a pocket formed by hydrophobic amino acids of transmembrane domains (TM) 1, 2, 6 and 7 of the Y1 receptor. To investigate which residues were required for ligand binding, we mutated the sequences encoding F41, L43, F96, Y100, F286 and H298 of the human Y1 receptor. The mutant cDNAs were transiently expressed in Hela cells and the ability of the encoded proteins to bind NPY was evaluated. Replacing F41, L43 or F96 with alanines had no effect on NPY binding. On the contrary, Y100, F286 and H298 appeared to be residues critical for ligand binding. In particular, the removal of the hydroxyl group of Y100 (Tyr100-->Phe100 mutation) yielded a protein devoid of affinity for the ligand. The level of expression and the presence on the cell surface of mutants lacking NPY binding activity was assessed by immunological techniques. In addition, we tested the ability of synthetic analogues of neuropeptide Y with substitutions at position 36 to bind to the Y1 receptor. To get spatial insight into the relative positions of the above mentioned residues we constructed a molecular model of the interaction between NPY:Y36 and the elements of the hydrophobic pocket surrounding this residue.
Mol Cell Endocrinol 1995 Aug 11
PMID:Role of a hydrophobic pocket of the human Y1 neuropeptide Y receptor in ligand binding. 748 25

Nicotine, a major pharmacologically active component of tobacco smoke, is generally believed to be one of the factors responsible for the deleterious consequences of cigarette smoking. Nicotine activates the sympathoadrenal system and increases the synthesis and release of catecholamines into circulation. In this study we show that single and repeated injections of nicotine increase the expression of tyrosine hydroxylase (TH), a rate limiting enzyme in the catecholamine biosynthetic pathway. These treatments also regulated the expression of dopamine beta-hydroxylase (DBH) and neuropeptide Y (NPY) in rat adrenals. The effect of nicotine on several transcription factors in the adrenal medulla was examined. Nicotine administration by injection increased the phosphorylation of CREB and induced c-Fos protein without affecting members of the jun family. In contrast to the results with injections, continuous infusion via osmotic pumps did not affect any of these parameters. These data indicate that activation of several transcription factors and increased expression of TH, DBH, and NPY is dependent on the mode of nicotine administration.
Brain Res Mol Brain Res 1995 Aug
PMID:Nicotine elicits changes in expression of adrenal catecholamine biosynthetic enzymes, neuropeptide Y and immediate early genes by injection but not continuous administration. 749 48

By in situ hybridization and immunohistochemistry, we examined the expression of neuropeptides such as neuropeptide Y (NPY), galanin (Gal), substance P (SP), vasoactive intestinal polypeptide (VIP) and their mRNAs in the rat mesencephalic trigeminal nucleus (Mes5) following masseteric nerve transection. On the side contralateral to the nerve transection, none of the peptides examined were labeled in Mes5 cell bodies. However, on the side ipsilateral to the lesion, NPY, Gal and preprotachykinin (PPT) mRNAs appeared in Mes5 cell bodies. Double labeling for mRNAs by in situ hybridization and retrograde tracer fluoro-gold (FG) revealed that almost all (96-97%) the FG-labeled neurons which were cut expressed NPY and Gal mRNAs, whereas less neurons (87%) expressed PPT mRNA. NPY and Gal-like immunoreactivities were detected in Mes5 cell bodies ipsilateral to the axotomy. The results suggested that these neuropeptides play roles in adaptive processes after peripheral nerve injury in Mes5 neurons as they are thought to do so in dorsal root ganglion neurons.
Brain Res Mol Brain Res 1994 Apr
PMID:The expression of neuropeptides and their mRNAs in the trigeminal mesencephalic nucleus following masseteric nerve transection. 751 33

We report the first systematic study on short peptide structure affinity and activity for the neuropeptide Y (NPY) receptor. A series of linear pentapeptides has been synthesized that display affinities in the low micromolar range toward rat brain NPY receptors. Furthermore, some of these compounds competitively antagonize the Y1-type NPY receptor-mediated increase in cytosolic Ca2+ in human erythroleukemic (HEL) cells. The inactive NPY carboxyl-terminal pentapeptide (Thr-Arg-Gln-Arg-Tyr-NH2; IC50 > 100 microM) was modified by replacing threonine with an aromatic amino acid and glutamine with leucine. This resulted in a series of pentapeptides with dramatically improved affinity (IC50 = 0.5-4 microM) for the rat brain receptor. The structure-affinity data suggest that these peptides may represent a noncontinuous epitope containing the amino-terminal tyrosine and the carboxyl-terminal residues Arg-35 and Tyr-36 of NPY.
Mol Pharmacol 1995 Sep
PMID:Structure-activity relationship of novel pentapeptide neuropeptide Y receptor antagonists is consistent with a noncontinuous epitope for ligand-receptor binding. 756 22

Neurotrophins, which are structurally related to nerve growth factor, have been shown to promote survival of various neurons. Recently, we found a novel activity of a neurotrophin in the brain: Brain-derived neurotrophic factor (BDNF) enhances expression of various neuropeptides. The neuropeptide differentiation activity was then compared among neurotrophins both in vivo and in vitro. In cultured neocortical neurons, BDNF and neurotrophin-5 (NT-5) remarkably increased levels of neuropeptide Y and somatostatin, and neurotrophin-3 (NT-3) also increased these peptides but required higher concentrations. At elevating substance P, however, NT-3 was as potent as BDNF. In contrast, NGF had negligible or no effect. Neurotrophins administered into neonatal brain exhibited slightly different potencies for increasing these neuropeptides: The most marked increase in neuropeptide Y levels was obtained in the neocortex by NT-5, whereas in the striatum and hippocampus by BDNF, although all three neurotrophins increased somatostatin similarly in all the brain regions examined. Overall spatial patterns of the neuropeptide induction were similar among the neurotrophins. Neurons in adult rat brain can also react with the neurotrophins and alter neuropeptide expression in a slightly different fashion. Excitatory neuronal activity and hormones are known to change expression of neurotrophins. Therefore, neurotrophins, neuronal activity, and hormones influence each other and all regulate neurotransmitter/peptide expression in developing and mature brain. Physiological implication of the neurotransmitter/peptide differentiation activities is also discussed.
Mol Neurobiol
PMID:Regulation of neuropeptide expression in the brain by neurotrophins. Potential role in vivo. 757 4

Neuronal peptides exert neurohormonal and neurotransmitter (neuromodulator) functions in the central nervous system (CNS). Besides these functions, a group of neuropeptides may have a capacity to create cell proliferation, growth, and survival. Axotomy induces transient (1-21 d) upregulation of synthesis and gene expression of neuropeptides, such as galanin, corticotropin releasing factor, dynorphin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, cholecystokinin, angiotensin II, and neuropeptide Y. These neuropeptides are colocalized with "classic" neurotransmitters (acetylcholine, aspartate, glutamate) or neurohormones (vasopressin, oxytocin) that are downregulated by axotomy in the same neuronal cells. It is more likely that neuronal cells, in response to axotomy, increase expression of neuropeptides that promote their survival and regeneration, and may downregulate substances related to their transmitter or secretory activities.
Mol Neurobiol
PMID:Neuropeptide messenger plasticity in the CNS neurons following axotomy. 757 12

The mouse adrenocortical Y-1 cell line has been found to express high affinity binding sites for neuropeptide Y (NPY). Pharmacological studies have shown that these NPY binding sites are of the Y1 type. Reverse transcription-polymerase chain reaction using primers specific for the rat Y1 receptor revealed that the NPY Y1 receptor mRNA is present in Y-1 cells. The Kd of the receptor for NPY was found to be 1.75 +/- 0.20 nM and the Bmax was 265 +/- 18 fmol/mg. The NPY Y1 receptors in this adrenocortical cell line were shown to be coupled to pertussis toxin-sensitive G proteins. Stimulation of Y1 receptors resulted in the inhibition of forskolin- and adrenocorticotropic hormone (ACTH)-stimulated cAMP synthesis. NPY had no effect on basal steroid release from the Y-1 cells. At an ACTH concentration of 0.1 microM, NPY did not affect ACTH-stimulated steroid release, although NPY did inhibit cAMP production under the same hormonal conditions. cAMP profoundly affected the density of the NPY receptors in Y-1 cells. Treatment of the cells with N6,2'-O-dibutyryl-cAMP or ACTH reduced the Y1 receptor density by > 50%. On the other hand the steroid dexamethasone increased the density of Y1 receptors by 35%. Although additional detailed studies are necessary, these results may have interesting implications for the functions of ACTH, steroids, and NPY in the pituitary-adrenocortical axis.
Mol Pharmacol 1995 Jul
PMID:Studies on neuropeptide Y receptors in a mouse adrenocortical cell line. 762 80

1. The pulsatile release of luteinizing hormone-releasing hormone (LHRH) is critical for reproductive function. However, the exact mechanism of LHRH pulse generation is unclear. The purpose of this article is to review the current knowledge on LHRH pulse generation and to discuss a series of studies in our laboratory. 2. Using push-pull perfusion in the stalk-median eminence of the rhesus monkey several important facts have been revealed. There is evidence indicating that LHRH neurons themselves have endogenous pulse-generating mechanisms but that the pulsatility of LHRH release is also modulated by input from neuropeptide Y (NPY) and norepinephrine (NE) neurons. The release of NPY and NE is pulsatile, with their pulses preceding or occurring simultaneously with LHRH pulses, and the neuroligands NPY and NE and their agonists stimulate LHRH pulses, while the antagonists of the ligands suppress LHRH pulses. 3. The pulsatile release of LHRH increases during the estrogen-induced LH surge as well as the progesterone-induced LH surge. These increases are partly due to the stimulatory effects of estrogen and progesterone on NPY neurons. 4. An increase in pulsatile LHRH release occurs at the onset of puberty. This pubertal increase in LHRH release appears to be due to the removal of tonic inhibition from gamma aminobutyric acid (GABA) neurons and a subsequent increase in the inputs of NPY and NE neurons to LHRH neurons. 5. There are indications that additional neuromodulators are involved in the control of the LHRH pulse generation and that glia may play a role in coordinating pulses of the release of LHRH and neuromodulators. 6. It is concluded that the mechanism generating LHRH pulses appears to comprise highly complex cellular elements in the hypothalamus. The study of neuronal and nonneuronal elements of LHRH pulse generation may serve as a model to study the oscillatory behavior of neurosecretion.
Cell Mol Neurobiol 1995 Feb
PMID:Control of luteinizing hormone-releasing hormone pulse generation in nonhuman primates. 764 6

We have investigated, by Northern blot analysis, the hypothalamic gene expression [messenger RNA (mRNA)] of two appetite stimulating neuropeptides, neuropeptide Y (NPY) and galanin (GAL) in lean (+/+) and genetically obese (fa/fa) Zucker rats at 11, 24 and 40 weeks of age and their responsiveness to food deprivation. At 11 weeks of age, hypothalamic NPY mRNA levels of fa/fa rats were similar to those observed in lean littermates. However, NPY mRNA levels of fa/fa rats were significantly greater than those of lean rats at 24 (+126%; P < 0.01) and 40 (+65%; P < 0.05) weeks of age. Food deprivation caused a significant increase in NPY mRNA levels in both lean and fa/fa Zucker rats at 11 and 24 weeks of age, but not at 40 weeks old rats. Hypothalamic GAL mRNA showed a different pattern of change. The relative content of GAL mRNA in 11 week old obese rats was significantly lower (-68%; P < 0.05) than that of lean rats, while GAL mRNA was significantly higher in 40 week old (+57%; P < 0.05) obese rats compared to their lean littermates. At 24 weeks of age, hypothalamic GAL mRNA levels did not differ between lean and obese rats. Food deprivation induced no change in hypothalamic GAL mRNA in lean rats of all 3 ages; however, it caused an increase of GAL mRNA in obese rats at 11 (+60%; P < 0.05) and 24 (+44%; P < 0.05) weeks, but not at 40 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1993 Aug
PMID:Critical effects of aging and nutritional state on hypothalamic neuropeptide Y and galanin gene expression in lean and genetically obese Zucker rats. 769 7


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