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1.
To differentiate NPY receptor subtypes, Y1 and Y2, in terms of their impact on feeding behavior, the intact molecule NPY(1–36) and the 3 fragments, NPY(2–36), the Y1 agonist [Leu31,Pro34]NPY, and the Y2 agonist NPY(13–36), were injected (100 pmol/0.3 μl) into the hypothalamic paraventricular nucleus (PVN) of freely feeding rats. A computer-automated data acquisition system was employed in these experiments to permit a detailed analysis of feeding over the 12-h nocturnal cycle, in animals maintained on pure macronutrient diets. The results demonstrate that: 1) NPY(1–36) potentiates feeding behavior, primarily carbohydrate ingestion, by increasing the size and duration of the first meal after injection, rather than by affecting meal number or feeding rate, suggesting that NPY acts through mechanisms of satiety. The potentiation of carbohydrate intake occurs in association with a suppression of protein intake, which is strongest during the second meal after injection and which further increases the proportion of carbohydrate in the diet. No changes in fat ingestion are seen. 2) NPY(2–36), with the N-terminal tyrosine residue deleted, is equally potent to NPY(1–36) in potentiating carbohydrate intake and increasing meal size; however, it is less selective than NPY(1–36), producing an additional, smaller increase in consumption of protein. 3) The stimulatory effect of these peptides on carbohydrate intake and meal size is similarly observed, with somewhat reduced potency, after PVN injection of the selective Y1 agonist [Leu31,Pro34]NPY which, like NPY(1–36), also reduces protein intake. 4) The Y2 receptor agonist, NPY(13–36), causes a decrease in the ingestion of carbohydrate, a smaller decline in protein intake, and a reduction in meal size. It is proposed that hypothalamic Y1 receptors mediate the stimulatory effect of NPY on carbohydrate intake and meal size, while Y2 receptors have the opposite effect of suppressing carbohydrate intake, possibly by altering presynaptic release of monoamines known to influence nutrient ingestion.  相似文献   

2.
In this in vitro study, we investigated the influence of neuropeptide Y (NPY) Y1 receptor activation or inhibition on the viability of cultured neuronal or glial cells following oxygen glucose deprivation (OGD). Viability of cultured cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. When compared to the vehicle-treated control group, treatment with NPY or [Leu31,Pro34]-NPY (Y1 agonist) reduced viability of cultured SK-N-MC (Y1-expressing) human neuronal cells at 24 h after 1 h of OGD, while BIBP3226 (Y1 antagonist) improved viability. Except at the highest concentration of NPY used in the study, treatment with NPY or NPY3-36 (Y2 agonist) did not influence viability of cultured SH-SY5Y (Y2-expressing) human neuronal cells at 24 h after 1 h of OGD. In addition, treatment with NPY, [Leu31,Pro34]-NPY, NPY3-36, or BIBP3226 did not affect viability of cultured primary astrocytes at 24 h after 4 h of OGD. The present results agree with those of a recent in vivo study. Activation of NPY-Y1 receptors may mediate ischemic pathophysiological processes, and inhibiting the Y1 receptors may be protective. The combination of OGD and cultured neuronal cells may be useful in future studies on the neuroprotective and harmful mechanisms of NPY-Y1 receptor inhibition and activation during ischemia, respectively.  相似文献   

3.
Abstract

Neuropeptide Y (NPY) recognition by the human neuroblastoma cell lines SiMa, Kelly, SH‐SY5Y, CHP‐234, and MHH‐NB‐11 was analyzed in radioactive binding assays using tritiated NPY. For the cell lines CHP‐234 and MHH‐NB‐11 binding of [3H]propionyl‐NPY was observed with Kd‐values of 0.64 ± 0.07 nM and 0.53 ± 0.12 nM, respectively, determined by saturation analysis with non‐linear regression. The receptor subtype was determined by competition analysis using the subtype selective NPY analogues [Leu31, Pro34]‐NPY (NPY‐Y1, NPY‐Y5), [Ahx5‐24]‐NPY (NPY‐Y2), [Ala31, Aib32]‐NPY (NPY‐Y5), NPY [3‐36] (NPY‐Y2, NPY‐Y5), and NPY [13‐36] (NPY‐Y2). Both cell lines, CHP‐234 and MHH‐NB‐11, the latter one being characterized for NPY receptors for the first time, showed exclusive expression of NPY‐Y2 receptors. In both cell lines binding of NPY induced signal transduction, which was monitored as reduction of forskolin‐induced cAMP production in an ELISA.  相似文献   

4.
Neuropeptide Y (NPY, 1–300 nM) mediated a concentration-dependent inhibition of field stimulation-evoked [3H]norepinephrine (NE) overflow from the isolated, superfused rabbit iris-ciliary body. At equimolar concentrations (100 nM), the homologous neuropeptide peptide YY (PYY) mimicked the effects of NPY, whereas pancreatic polypeptide (PP) and the C-terminal fragment of NPY16–36 did not modify [3H]NE release. NPY-induced inhibition of [3H]NE release was unaffected by pretreatment of tissues with atropine (100 nM) plus yohimbine (100 nM) and was nonadditive with the maximal prejunctional effects of carbamycholine or clonidine, indicating that NPY acts independently of prejunctional muscarinic or alpha2-adrenergic receptor activity to reduce [3H]NE overflow. It is concluded that NPY is a specific, potent modulator of adrenergic neurosecretion in the rabbit iris-ciliary body. These findings confirm the role of NPY as a co-transmitter at ocular sympathetic neuroeffector junctions, either mimicking or augmenting the actions of endogenously released norepinephrine.To whom to address reprint requests.  相似文献   

5.
Neuropeptide Y (NPY) is expressed in mammalian retina but the location and potential modulatory effects of NPY receptor activation remain largely unknown. Retinal ganglion cell (RGC) death is a hallmark of several retinal degenerative diseases, particularly glaucoma. Using purified RGCs and ex vivo rat retinal preparations, we have measured RGC intracellular free calcium concentration ([Ca2+]i) and RGC spiking activity, respectively. We found that NPY attenuated the increase in the [Ca2+]i triggered by glutamate mainly via Y1 receptor activation. Moreover, (Leu31, Pro34)−NPY, a Y1/Y5 receptor agonist, increased the initial burst response of OFF-type RGCs, although no effect was observed on RGC spontaneous spiking activity. The Y1 receptor activation was also able to directly modulate RGC responses by attenuating the NMDA-induced increase in RGC spiking activity. These results suggest that Y1 receptor activation, at the level of inner or outer plexiform layers, leads to modulation of RGC receptive field properties. Using in vitro cultures of rat retinal explants exposed to NMDA, we found that NPY pretreatment prevented NMDA-induced cell death. However, in an animal model of retinal ischemia-reperfusion injury, pretreatment with NPY or (Leu31, Pro34)−NPY was not able to prevent apoptosis or rescue RGCs. In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs. However, further studies are needed to evaluate whether NPY neuroprotective actions detected in retinal explants can be translated into animal models of retinal degenerative diseases.  相似文献   

6.
Agmatine and neuropeptide Y (NPY) are widely distributed in central nervous system and critically involved in modulation of depressive behavior in experimental animals. However their mutual interaction, if any, in regulation of depression remain largely unexplored. In the present study we explored the possible interaction between agmatine and neuropeptide Y in regulation of depression like behavior in forced swim test. We found that acute intracerebroventricular (i.c.v.) administration of agmatine (20–40 μg/rat), NPY (5 and 10 μg/rat) and NPY Y1 receptor agonist, [Leu31, Pro34]-NPY (0.4 and 0.8 ng/rat) dose dependently decreased immobility time in forced swim test indicating their antidepressant like effects. In combination studies, the antidepressant like effect of agmatine (10 μg/rat) was significantly potentiated by NPY (1 and 5 μg/rat, icv) or [Leu31, Pro34]-NPY (0.2 and 0.4 ng/rat, icv) pretreatment. Conversely, pretreatment of animals with NPY Y1 receptor antagonist, BIBP3226 (0.1 ng/rat, i.c.v.) completely blocked the antidepressant like effect of agmatine (20–40 μg/rat) and its synergistic effect with NPY (1 μg/rat, icv) or [Leu31, Pro34]-NPY (0.2 ng/rat, icv). The results of the present study showed that, agmatine exerts antidepressant like effects via NPYergic system possibly mediated by the NPY Y1 receptor subtypes and suggest that interaction between agmatine and neuropeptide Y may be relevant to generate the therapeutic strategies for the treatment of depression.  相似文献   

7.
Neuropeptide Y is one of the most abundant neuropeptides in the central and peripheral nervous systems and its sequence is highly conserved among species. A number of key physiological roles for NPY are now emerging, especially in the control of feeding and energy homeostasis. Other physiological actions of NPY are also reviewed. The metabolism of NPY has been examined by employing certain purified ectopeptidases and by using different membrane preparations. These approaches reveal that NPY is processed at its N-terminus by two proline-preferring aminopeptidases: aminopeptidase P and dipeptidyl peptidase IV. The action of the latter enzyme generates NPY (3−36) which has previously been shown to be a selective agonist at the Y2 class of NPY receptor. Thus, post-secretory processing of NPY can modify receptor selectivity. NPY is found to be resistant to the action of two other membrane aminopeptidases (N and W), and to the action of angiotensin converting enzyme. However, it is a substrate for endopeptidase-24.11 (K m=15.4 μM) which can cleave the Tyr20−Tyr21 and Leu30−Ile31 bonds consistent with the known specificity of the enzyme. In striatal synaptic and renal brush border membranes, NEP is shown to be the major NPY hydrolysing activity but plays a lesser role in intestinal brush border membranes. Knowledge of the proteolytic processing of NPY should aid in the design of stable analogues of this neuropeptide. Special issue dedicated to Dr. Herman Bachelard.  相似文献   

8.
The human NPY Y1 receptor undergoes fast agonist-induced internalization via clathrin-coated pits then recycles back to the cell membrane. In an attempt to identify the molecular determinants involved in this process, we studied several C-terminal truncation mutants tagged with EFGP. In the absence of agonist, Y1 receptors lacking the last 32 C-terminal amino acids (Y1Δ32) are constitutively internalized, unlike full-length Y1 receptors. At steady state, internalized Y1Δ32 receptors co-localize with transferrin, a marker of early and recycling endosomes. Inhibition of constitutive internalization of Y1Δ32 receptors by hypertonic sucrose or by co-expression of Rab5aS34N, a dominant negative form of the small GTPase Rab5a or depletion of all three isoforms of Rab5 indicates the involvement of clathrin-coated pits. In contrast, a truncated receptor lacking the last 42 C-terminal amino acids (Y1Δ42) does not constitutively internalize, consistent with the possibility that there is a molecular determinant responsible for constitutive internalization located in the last 10 amino acids of Y1Δ32 receptors. We show that the agonist-independent internalization of Y1Δ32 receptors involves a tyrosine-based motif YXXΦ. The potential role of this motif in the behaviour of full-length Y1 receptors has also been explored. Our results indicate that a C-terminal tyrosine-based motif is critical for the constitutive internalization of truncated Y1Δ32 receptors. We suggest that this motif is masked in full-length Y1 receptors which do not constitutively internalize in the absence of agonist.  相似文献   

9.
NPY receptors are identified in calf frontal cortex and hippocampus membrane preparations by binding of N-[propionyl-3H] neuropeptide Y. Saturation and competition binding data with PYY, NPY-(18–36) and NPY itself fit with a single class of sites: for the radioligand KD = 1.4 ± 0.5 nM, Bmax = 434 ± 180 fmol/mg protein in frontal cortex, KD = 0.7 ± 0.2 nM, Bmax = 267 ± 50 fmol/mg protein in hippocampus. Competition curves of the Y1-subtype selective agonist [Leu31, Pro34]NPY are biphasic in both membrane preparations: high affinity sites (i.e. Y1-subtype) amount to 80% in frontal cortex and 23% in hippocampus. The remaining sites are of the Y2-subtype. Out of 23 Conus venom preparations, 17 inhibit the binding of [3H]NPY in both membrane preparations, but only two of them (from Conus aulicus and C. pennaceus) do so with high potency (ic50 < 5 μg protein/ml). Only one venom preparation (from C. mercator) had weak discriminatory properties (ic50Y2/ic50Y1 = 6). Venom from C. anemone increased the [3H]NPY binding 5-fold and with an ic50 of 15–18 μg protein/ml. This binding occurred to the venom itself and was unrelated to the NPY receptors since it was equally potent when displaced by [Leu31, Pro34]NPY, NPY-(18–36), PYY and NPY. Copyright © 1996 Elsevier Science Ltd  相似文献   

10.
Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) belong to the NPY hormone family and activate a class of receptors called the Y‐receptors, and also belong to the large superfamily of the G‐protein coupled receptors. Structure–affinity and structure–activity relationship studies of peptide analogs, combined with studies based on site‐directed mutagenesis and anti‐receptor antibodies, have given insight into the individual characterization of each receptor subtype relative to its interaction with the ligand, as well as to its biological function. A number of selective antagonists at the Y1‐receptor are available whose structures resemble that of the C‐terminus of NPY. Some of these compounds, like BIBP3226, BIBO3304 and GW1229, have recently been used for in vivo investigations of the NPY‐induced increase in food intake. Y2‐receptor selective agonists are the analog cyclo‐(28/32)‐Ac‐[Lys28‐Glu32]‐(25–36)‐pNPY and the TASP molecule containing two units of the NPY segment 21–36. Now the first antagonist with nanomolar affinity for the Y2‐receptor is also known, BIIE0246. So far, the native peptide PP has been shown to be the most potent ligand at the Y4‐receptor. However, by the design of PP/NPY chimera, some analogs have been found that bind not only to the Y4‐, but also to the Y5‐receptor with subnanomolar affinities, and are as potent as NPY at the Y1‐receptor. For the characterization of the Y5‐receptor in vitro and in vivo, a new class of highly selective agonists is now available. This consists of analogs of NPY and of PP/NPY chimera which all contain the motif Ala31‐Aib32. This motif has been shown to induce a 310‐helical turn in the region 28–31 of NPY and is suggested to be the key motif for high Y5‐receptor selectivity. The results of feeding experiments in rats treated with the first highly specific Y5‐receptor agonists support the hypothesis that this receptor plays a role in the NPY‐induced stimulation of food intake. In conclusion, the selective compounds for the different Y‐receptor subtypes known so far are promising tools for a better understanding of the physiological properties of the hormones of the NPY family and related receptors. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   

11.
Selective NPY analogues are potent tools for tumour targeting. Their Y1‐receptors are significantly over‐expressed in human breast tumours, whereas normal breast tissue only expresses Y2‐receptors. The endogenous peptide consists of 36 amino acids, whereas smaller peptides are preferred because of better labelling efficiencies. As Y1‐receptor agonists enhance the tumour to background ratio compared to Y1‐receptor antagonists, we were interested in the development of Y1‐receptor selective agonists. We designed 19 peptides containing the C‐terminus of NPY (28–36) with several modifications. By using competition receptor binding affinity assays, we identified three NPY analogues with high Y1‐receptor affinity and selectivity. Metabolic stability studies in human blood plasma of the N‐terminally 5(6)‐carboxyfluorescein (CF) labelled peptides resulted in half‐lives of several hours. Furthermore, the degradation pattern revealed proteolytic degradation of the peptides by amino peptidases. The most promising peptide was further investigated in receptor activation and internalization studies. Signal transduction assays revealed clear agonistic properties, which could be confirmed by microscopy studies that showed clear Y1‐receptor internalization. For the first time, here we show the design and characterization of a small Y1‐receptor selective agonist. This agonist might be a useful novel ligand for NPY‐mediated tumour diagnostics and therapeutics. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   

12.
Kumar S  Rai U 《Peptides》2011,32(6):1324-1329
Present in vitro study in the wall lizard Hemidactylus flaviviridis, for the first time in ectothermic vertebrates, demonstrated the immunoregulatory role of neuropeptide Y (NPY) and its receptor-coupled downstream signaling cascade. NPY inhibited the percentage phagocytosis and phagocytic index of splenic phagocytes. The inhibitory effect of NPY on phagocytosis was completely antagonized by Y2 and Y5 receptor antagonists. This suggests that NPY mediated its effect on phagocytosis through Y2 and Y5 receptors. Further, NPY receptor-coupled downstream signaling cascade for NPY effect on phagocytosis was explored using the inhibitors of adenylate cyclase (SQ 22536) and protein kinase A (H-89). The SQ 22536/H-89 in a concentration-related manner decreased the inhibitory effect of NPY on phagocytosis. Further, an increase in intracellular cAMP level was observed in response to NPY. Taken together, it can be concluded that NPY via Y2 and Y5 receptor-coupled AC-cAMP-PKA pathway downregulated the phagocytic activity of lizard splenic phagocytes.  相似文献   

13.
The binding characteristics of [3H]-NPVF and [3H]-EYF, the two first tritiated probes for the respective labelling of NPFF1 and NPFF2 receptors, are presented. In membranes from CHO cells transfected with the human NPFF1 receptor, [3H]-NPVF labelled one class of binding sites with a high affinity (Bmax = 4 pmol/mg protein, Kd = 2.65 nM). In membranes from CHO cells transfected with the human NPFF2 receptor, [3H]-EYF labelled one class of binding sites with a high affinity (Bmax = 16 pmol/mg protein, Kd = 0.54 nM). Both radioligands exhibited time-dependent binding, low (10–20%) non-specific binding and poor cross-reactivity towards the related receptor subtype. The potency of different NPFF ligands to displace [3H]-NPVF and [3H]-EYF binding profiles was in good agreement with the profile previously measured by using 125I-probes (NPFF1 receptor: NPVF ≥ 1DMe = SPA-NPFF > NPFF = SQA-NPFF = QFW-NPSF > NPSF > RF9; NPFF2 receptor: SPA-NPFF > > SQA-NPFF = QFW-NPSF = 1DMe = NPFF  NPSF = NPVF > RF9). Therefore, [3H]-NPVF and [3H]-EYF are new valuable tools for performing binding on NPFF receptors.  相似文献   

14.
The primary structures of three brewer's yeast tRNAs: tRNAPro2 and tRNAHis1 and 2 have been determined
The U* in the anticodon U*-G-G of tRNAPro2 is probably a derivative of U; tRNAPro2 has 80 per cent homology with mammalian tRNAsPro. tRNAHis1 and tRNAHis2 differ by only 5 nucleotides; they have identical anticodons and may therefore recognize both codons for histidine; they have an additional nucleotide at the 5′ end. As in all other sequenced tRNAsHis this nucleotide is not paired with the fourth nucleotide from acceptor adenosine. All three sequenced tRNAs have a low degree of homology with their counterparts from yeast mitochondria.  相似文献   

15.
Receptors for neuropeptide Y (NPY) and peptide YY (PYY) have been extensively characterized in the brain. Less is known about NPY receptor subtypes in the spleen, though it is well established that NPY produces vascular contraction in this tissue. In the present study, we found an unusually high density of Y1 receptors in the guinea pig spleen. These receptors are localized to the red pulp and exhibit a pharmacology that is consistent with the Y1 receptor. On the other hand, only very low densities for Y2 receptors were observed. Therefore, the guinea pig spleen may be a ideal tissue for further study of the role of Y1 receptors in cardiovascular and immune function.  相似文献   

16.
Abstract

Porcine neuropeptide Y (NPY), a 36 amino acid hormone of the pancreatic polypeptide family, and subtype selective analogues have been synthesized by solid phase peptide synthesis. The peptides were labelled with Cy3TM, a commercially available fluorescent marker based on a cyanine dye, by solid phase strategy. During the cleavage α partial fragmentation of the fluorescent marker occurred. This has been investigated by means of HPLC and electrospray mass spectrometry. The labelled analogues of NPY showed high affinity to the NPY receptor subtypes Y1 and Y2. Thus, Cy3-NPY. Y1-selective Cy3-[Pro34] NPY and Y2 selective Cy3-[Ahx5–24] NPY were used to label SK-N-MC- and SMS-KAN-cells, which are stably expressing the Y1-(SK-N-MC) and the Y2-receptor subtype (SMS-KAN). The binding of the labelled analogues to the receptors was reversible and specific. The photoactivatable analogue, [(Tmd)Phe27] NPY, which showed high affinity to both receptor subtypes was labelled with Cy3 in solution. Whereas the fluorescent labelling of the cells with analogues without photoactivatable amino acid was reversible, successful photocrosslinking could be investigated by the irreversible staining of the cells using Cy3-[(Tmd)Phe27] NPY. These subtype selective analogues are exciting tools to trace receptors in tissues and to identify the pharmacologically characterized subtypes without radioactivity.  相似文献   

17.
Abstract

Neuropeptide Y (NPY), receptors belong to the G-protein coupled receptor superfamily. NPY mediates several physiological responses, such as blood pressure, food intake, sedation. These actions of NPY are mediated by six receptor subtypes denoted as Y1-Y5 and y6. Modeling of receptor subtypes and binding site identification is an important step in developing new therapeutic agents. We have attempted to model the three NPY receptor types, Y1, Y4, and Y5 using homology modeling and threading methods. The models are consistent with previously reported experimental evidence. To understand the interaction and selectivity of NPY analogues with different neuropeptide receptors, docking studies of two neuropeptide analogues (BVD10 and BVD15) with receptors Y1 and Y4 were carried out. Results of the docking studies indicated that the interaction of ligands BVD10 and BVD15 with Y1 and Y4 receptors are different. These results were evaluated for selectivity of peptide analogues BVD10 and BVD15 towards the receptors.  相似文献   

18.
Previous studies have identified the (4–10) heptapeptide sequence as the central core of α-MSH/ACTH peptides required for mediation of important biological activities. In the present study, the structure-activity relationships of Nle4-substituted and -bridged cyclic α-MSH analogues, which were previously shown to exhibit a wide range of melanotropic potencies from weak agonism to super potency, were examined for grooming behavioral activity in the rat following intracerebroventricular injections. The results showed that stepwise C-terminal elongation of the linear Nle4-substituted Ac-α-MSH4–10-NH2 increased grooming potencies of the peptides in a manner similar to their actions on melanocytes. The most interesting finding was the observation that cyclization of the inactive linear “central (4–10) core” of α-MSH (Ac-α-MSH4–10) to form Ac-[ ]-α-MSH4–10-NH2 resulted in a super potent agonist in the grooming assay. However, while cyclization of the (4–10) heptapeptide produced potent agonists on grooming behavior, the structure-activity relationships were different than the frog skin bioassay. These findings support the hypothesis that appropriate structural and confirmational modifications of α-MSH-related peptides can produce profound effects on the bioactivities of the peptides, and suggest that different structural-conformational requirements exist for α-MSH interactions with its various receptors.  相似文献   

19.
It has been claimed that glutamate excitotoxicity might have a role in the pathogenesis of several retinal degenerative diseases, including glaucoma and diabetic retinopathy. Neuropeptide Y (NPY) has neuroprotective properties against excitotoxicity in the hippocampus, through the activation of Y1, Y2 and/or Y5 receptors. The principal objective of this study is to investigate the potential protective role of NPY against glutamate-induced toxicity in rat retinal cells (in vitro and in an animal model), unraveling the NPY receptors and intracellular mechanisms involved. Rat retinal neural cell cultures were prepared from newborn Wistar rats (P3-P5) and exposed to glutamate (500 μM) for 24 h. Necrotic cell death was evaluated by propidium iodide (PI) assay and apoptotic cell death using TUNEL and caspase-3 assays. The cell types present in culture were identified by immunocytochemistry. The involvement of NPY receptors was assessed using selective agonists and antagonists. Pre-treatment of cells with NPY (100 nM) inhibited both necrotic cell death (PI-positive cells) and apoptotic cell death (TUNEL-positive cells and caspase 3-positive cells) triggered by glutamate, with the neurons being the cells most strongly affected. The activation of NPY Y2, Y4 and Y5 receptors inhibited necrotic cell death, while apoptotic cell death was only prevented by the activation of NPY Y5 receptor. Moreover, NPY neuroprotective effect was mediated by the activation of PKA and p38K. In the animal model, NPY (2.35 nmol) was intravitreally injected 2 h before glutamate (500 nmol) injection into the vitreous. The protective role of NPY was assessed 24 h after glutamate (or saline) injection by TUNEL assay and Brn3a (marker of ganglion cells) immunohistochemistry. NPY inhibited the increase in the number of TUNEL-positive cells and the decrease in the number of Brn3a-positive cells induced by glutamate. In conclusion, NPY and NPY receptors can be considered potential targets to treat retinal degenerative diseases, such as glaucoma and diabetic retinopathy.  相似文献   

20.
Abstract: Neuropeptide Y (NPY) appears to be involved in the sympathetic regulation of vascular tone. To assess the putative role of NPY in mesenteric circulation, the release and biological effect of NPY were examined after electrical stimulation of perimesenteric arterial nerves. Nerve stimulation with trains of 2–30 Hz increased the perfusion pressure of the arterially perfused rat mesenteric bed in a frequency- and time-dependent fashion. Trains of 15–30 Hz significantly displaced to the left, approximately threefold, the noradrenaline (NA)-induced pressor concentration-response curve, in addition to increasing significantly its efficacy. Perfusion with 10 nM exogenous NPY mimicked the electrical stimulation effect, causing a threefold leftward shift of the NA concentration-response curve and increasing the maximal NA response. These effects were antagonized by 100 nM BIBP 3226, indicating the activity of NPY-Y1 receptors. Electrical stimulation of the perimesenteric nerves released immunoreactive NPY (ir-NPY) in a frequency-dependent fashion; the ir-NPY coelutes with synthetic NPY as confirmed by HPLC. Both the electrically induced pressor response and the calcium-dependent release of NPY were obliterated in preparations perfused with 1 µM guanethidine or in rats pretreated intravenously for 48 h with 6-hydroxydopamine, thus revealing the sympathetic origin of these phenomena. Only a small proportion of the total NPY content in the perimesenteric arterial nerves is released after electrical stimulation. Chromatographic studies of the physiological sources of the ir-NPY support that NPY fragments are generated via peptidase degradation. The present findings demonstrate that NPY is released from the perimesenteric arterial sympathetic nerves and acts, via the activation of NPY-Y1 receptors, as the mediator responsible for the potentiation of NA's effect on perfusion pressure in the isolated rat mesenteric bed.  相似文献   

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