Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA clone homologous with the human neuropeptide Y (NPY)-Y2 receptor has been isolated from a mouse brain cDNA library. Analysis of the predicted amino-acid sequence indicates that the polypeptide encoded by this cDNA is 94% homologous to the human NPY-Y2 receptor. In Chinese hamster ovary (CHO) cells expressing the mouse NPY-Y2 receptor, an increase in intracellular Ca2+ and inhibition of forskolin-induced cAMP accumulation were observed due to stimulation with NPY, NPY-(13-36) and peptide YY, but not with pancreatic polypeptide or [Leu31, Pro34]NPY. The fact that the NPY-induced increase in intracellular Ca2+ and inhibition of forskolin-induced cAMP accumulation were eliminated by pretreatment with pertussis toxin suggests that the NPY-Y2 receptor couples to PTX-sensitive G-protein(s), probably Gi/Go, in CHO cells.
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PMID:Cloning and functional expression of a cDNA encoding a mouse type 2 neuropeptide Y receptor. 891 76

1. In this study we have investigated neuropeptide Y (NPY) and somatostatin (SRIF) receptor-mediated elevation of intracellular Ca2+ concentration ([Ca2+]i) in the human neuroblastoma cell line SH-SY5Y. 2. The Ca(2+)-sensitive dye fura 2 was used to measure [Ca2+]i in confluent monolayers of SH-SY5Y cells. Neither NPY (30-100 nM) nor SRIF (100 nM) elevated [Ca2+]i when applied alone. However, when either NPY (300 pM-1 microM) or SRIF (300 pM-1 microM) was applied in the presence of the cholinoceptor agonist carbachol (1 microM or 100 microM) they evoked an elevation of [Ca2+]i above that caused by carbachol alone. 3. The elevation of [Ca2+]i by NPY was independent of the concentration of carbachol. In the presence of 1 microM or 100 microM carbachol NPY elevated [Ca2+]i with a pEC50 of 7.80 and 7.86 respectively. 4. In the presence of 1 microM carbachol the NPY Y2 selective agonist peptide YY(3-36) (PYY(3-36)) elevated [Ca2+]i with a pEC50 of 7.94, the NPY Y1 selective agonist [Leu31, Pro34]-NPY also elevated [Ca2+]i when applied in the presence of carbachol, but only at concentrations > 300 nM. The rank order of potency, PYY(3-36) > or = NPY > > [Leu31, Pro34]-NPY indicates that an NPY Y2-like receptor is involved in the elevation of [Ca2+]i. 5. In the presence of 1 microM carbachol, SRIF elevated [Ca2+]i with a pEC50 of 8.24. The sst2 receptor-preferring analogue BIM-23027 (c[N-Me-Ala-Tyr-D-Trp-Lys-Abu-Phe]) elevated [Ca2+]i with a pEC50 of 8.63, and the sst5-receptor preferring analogue L-362855 (c[Aha-Phe-Trp-D-Trp-Lys-Thr-Phe]) elevated [Ca2+]i with a pEC50 of approximately 6.1. Application of the sst3 receptor-preferring analogue BIM-23056 (D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2, 1 microM) to SH-SY5Y cells in the presence of carbachol neither elevated [Ca2+]i nor affected the elevations of [Ca2+]i caused by a subsequent coapplication of SRIF. The rank order of potency, BIM-23026 > or = SRIF > > L-362855 > > > BIM-23026 suggests that an sst2-like receptor is involved in the elevation of [Ca2+]i. 6. Block of carbachol activation of muscarinic receptors with atropine (1 microM) abolished the elevation of [Ca2+]i by the SRIF and NPY. 7. Muscarinic receptor activation, not a rise in [Ca2+]i, was required to reveal the NPY or SRIF response. The Ca2+ channel activator maitotoxin (2 ng ml-1) also elevated [Ca2+]i but subsequent application of either NPY or SRIF in the presence of maitotoxin caused no further changes in [Ca2+]i. 8. The elevations of [Ca2+]i by NPY and SRIF were abolished by pretreatment of the cells with pertussis toxin (200 ng-ml-1, 16 h). This treatment did not significantly affect the response of the cells to carbachol. 9. NPY and SRIF appeared to elevate [Ca2+]i by mobilizing Ca2+ from intracellular stores. Both NPY and SRIF continued to elevate [Ca2+]i when applied in nominally Ca(2+)-free external buffer. Thapsigargin (100 nM), an agent which discharges intracellular Ca2+ stores, also blocked the NPY and SRIF elevations of [Ca2+]i. 10. Delta-Opioid receptor agonists applied in the presence of carbachol also elevate [Ca2+]i in SH-SY5Y cells. When NPY (30 nM) or SRIF (100 nM) was applied together with a maximally effective concentration of the delta-opioid receptor agonist DPDPE ([D-Pen2,5]-enkephalin) (1 microM), the resulting elevations of [Ca2+]i were not greater than those caused by application of DPDPE alone. 11. Thus, in SH-SY5Y cells, NPY and SRIF can mobilize Ca2+ from intracellular stores via activation of NPY Y2 and sst2-like receptors, respectively. Neither NPY nor SRIF elevated [Ca2+]i when applied alone. The requirements for the elevations of [Ca2+]i by NPY and SRIF are the same as those for delta- and mu-opioid receptor and nociceptin receptor mobilization of [Ca2+]i in SH-SY5Y cells.
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PMID:Neuropeptide Y Y2 receptor and somatostatin sst2 receptor coupling to mobilization of intracellular calcium in SH-SY5Y human neuroblastoma cells. 903 49

Bovine chromaffin cells contain high affinity NPY binding sites coupled through a pertussis toxin-sensitive G protein to inhibition of cAMP accumulation. NPY alone does not alter [3H]inositol phosphate formation from [3H]phosphoinositides in these cells. Increasing NPY concentrations, in the presence of ATP (300 microM), produced a dose-dependent enhancement in [3H]-inositol phosphate formation, EC50 = 3.2 nM. Inclusion of the selective NPY-Y1 receptor antagonist BW1229 (1 microM) produced a marked decrease in NPY potency (EC50 = 3.3 microM). The Y1 receptor agonist, [Leu31, Pro34]-NPY, was equally effective with NPY, whereas NPY18-36, a Y2 receptor agonist, was much less effective. Inclusion of NPY with ATP also produced an enhancement in the release of intracellular Ca2+. The ability of NPY to enhance both [3H]inositol phosphate formation and the release of intracellular Ca2+ was pertussis toxin-insensitive. NPY action on bovine chromaffin cell receptor(s) appears to facilitated by different G proteins: one which can inhibit cAMP accumulation via a pertussis toxin-sensitive process and another which can enhance ATP activation of the inositol phosphate signaling pathway by a pertussis toxin-insensitive process.
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PMID:Neuropeptide Y enhances ATP-induced formation of inositol phosphates in chromaffin cells. 934 12

We examined the ability of rat Y1, Y2 and Y4 neuropeptide Y (NPY) receptors to regulate K+ and Ca++ channels expressed in Xenopus oocytes and HEK 293 cells, respectively. Stimulation of all three receptors with NPY or related peptides activated inwardly rectifying K+ currents resulting from the expression of rat GIRK1/CIR in frog oocytes. These effects were inhibited by pertussis toxin treatment. The effects of activating Y1 receptors were antagonized competitively by BIBP3226, SR120819A and GW1229. The effects of Y2 receptor activation were not blocked by these drugs, and the effects of Y4 receptor activation were only blocked by GW1229. Activation of all three NPY receptors also inhibited human alpha-1B Ca++ channels stably expressed in HEK293 cells. The effects of agonists at all three receptors were blocked by pertussis toxin treatment and were voltage dependent. Activation of all three types of NPY receptors produced much smaller inhibition of human alpha-1E Ca++ channels also stably expressed in HEK293 cells. These results suggest that NPY receptors can regulate K+ and Ca++ channels and that these effects may be responsible for the observed effects of NPY on neuronal excitability and synaptic transmission.
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PMID:Regulation of K+ and Ca++ channels by a family of neuropeptide Y receptors. 945 7

Neuropeptide Y and peptide YY are important central and peripheral modulators of cardiovascular and neuroendocrine functions, that act through multiple receptor subtypes, Y1 through Y5. A neuropeptide Y-binding site of the Y2 type was characterized by ligand-binding studies in isolated nerve terminals from the rat neurohypophysis. Functionally, neuropeptide Y and peptide YY dose-dependently triggered arginine 8-vasopressin and oxytocin release from perfused isolated terminals, and potentiated the arginine-8-vasopressin release induced by depolarization. Osmotic stimulation by salt loading of rats for two and seven days caused a more than three-fold increase in the neuropeptide Y content of the nerve endings. However, the Y2 receptor expression and arginine-8-vasopressin content declined, showing that the neuropeptide Y system is dynamic and suggesting that it plays a physiological role in salt and water homeostasis. Two sets of observations suggest the arginine-8-vasopressin release by neuropeptide Y may not be explained by neuropeptide Y effects on intracellular Ca2+. First, absence of Ca2+ from the perfusion medium did not affect the arginine-8-vasopressin release, and secondly neuropeptide Y did not change intraterminal Ca2+ concentrations. Pretreatment with pertussis toxin blocked arginine-8-vasopressin secretion by neuropeptide Y, suggesting activation of Gi or Go heterotrimeric G-proteins are required for secretion. It is concluded, that the nerve endings of the neurohypophysis contain a complete neuropeptide Y system with ligand and receptors. Neuropeptide Y may act in an autocrine fashion via activation of Y2 neuropeptide Y receptors to stimulate the release of vasopressin and oxytocin via a Gi/Go dependent secretory mechanism.
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PMID:Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release. 948 7

mIMCD-k2 cells are derived from the inner medullary collecting duct of a mouse and exhibit electrogenic sodium absorption and cAMP- and vasopressin (AVP)-stimulated electrogenic chloride secretion [N. L. Kizer, B. Lewis, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995; and N. L. Kizer, D. Vandorpe, B. Lewis, B. Bunting, J. Russell, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861, 1995]. The purpose of the present study was to determine how peptide YY (PYY) affects electrogenic Na+ and Cl- current in mIMCD-k2 cells. Short-circuit currents (Isc) were measured across monolayers of mIMCD-k2 cells mounted in Ussing-type chambers. PYY did not alter baseline Isc, nor did it alter Isc in chloride-free conditions, indicating no effect on electrogenic sodium transport. Baseline chloride current in these cells is low; therefore, chloride short-circuit current (IClsc) was stimulated with AVP (10 nM) added to the basolateral surface and 10 microM amiloride added to the apical surface. Although apical applications of PYY had no effect, basolateral application of PYY caused attenuation of IClsc, with the maximal inhibitory dose (100 nM) causing 52 +/- 1.3% inhibition (IC50 = 0.11 nM). Inhibition by PYY of IClsc is mediated through the Y2 receptor subtype, as PYY-(3-36) was the only PYY analog tested that caused inhibition and was equipotent to PYY. Inhibition by PYY of IClsc was abolished following incubation with pertussis toxin. We also show that PYY inhibits AVP-stimulated cAMP accumulation, with a maximal inhibitory dose (100 nM) causing a 38% +/- 6% inhibition (IC50 = 0.16 nM), comparable to inhibition by PYY of IClsc. We conclude that PYY acts through either Gi or Go to inhibit adenylate cyclase activity, leading to a decrease in AVP-stimulated chloride current.
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PMID:Peptide YY inhibits vasopressin-stimulated chloride secretion in inner medullary collecting duct cells. 972 20

Neuropeptide Y (NPY) regulates cardiovascular function, smooth muscle contraction and smooth muscle cell proliferation. Stimulation of NPY Y1 and Y2 receptor subtypes has been shown to result in increases in second messengers, such as cytosolic calcium concentrations, which precede physiological events such as cell contraction. To assess whether NPY receptors also stimulate second messengers which may precede mitogenic effects, we measured the mitogen-activated protein kinase (MAPK) activity in NPY receptor-expressing cell lines in response to NPY. CHO K1 cells stably expressing either NPY Y1 or Y2 receptors were shown to specifically bind radiolabelled Peptide YY (PYY), and MAPK activity in these cells was assessed using a peptide kinase assay. NPY stimulated dose-dependent increases in MAPK activity in both NPY Y1 and Y2 receptor-expressing cell lines. The NPY-stimulated MAPK activity was sensitive to pretreatment with pertussis toxin, the MAPK specific inhibitor PD098059 or wortmannin, an inhibitor of phosphatidylinositol-3-kinase (PI-3-K). These results indicate that both NPY Y1 and Y2 receptors stimulate wortmannin-sensitive increases in MAPK activity via Gi proteins and suggest a role for NPY Y1 and Y2 receptors in the regulation of smooth muscle cell growth involved in hypertrophy.
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PMID:Neuropeptide Y Y1 and Y2 receptor-mediated stimulation of mitogen-activated protein kinase activity. 980 11

Neuropeptide Y (NPY) regulates neurotransmitter release through activation of the Y2 receptor subtype. We have recently characterized a human glioblastoma cell line, LN319, that expresses exclusively NPY Y2 receptors and have demonstrated that NPY triggers transient decreases in cAMP and increases in intracellular calcium responses. The present study was designed to further characterize calcium signalling by NPY and bradykinin (BK) in LN319 cells. Both agonists elevated free intracellular calcium ([Ca(2+)](i)) without soliciting calcium influx. NPY appeared to activate two distinct signalling cascades that liberate calcium from thapsigargin- and ryanodine-insensitive compartments. One pathway proceeded through phospholipase C (PLC)-dependent phosphatidylinositol turnover, while the other triggered calcium release through a so far unidentified mediator. Part of the response was sensitive to pertussis toxin (PTX) under conditions where the toxin totally abolished the NPY-mediated effects on cAMP. The calcium release induced by BK on the other hand was largely PTX-insensitive, PLC-dependent, and from both thapsigargin- and ryanodine-sensitive stores. Following stimulation with NPY, subsequent [Ca(2+)](i) responses to NPY were strongly depressed. Partial heterologous desensitization occurred, when BK was used as the first agonist, whereas NPY had no effect on a subsequent stimulation with BK. These data suggest that NPY-induced calcium mobilization in LN319 cells involves two different G proteins and signalling mediators, and a hitherto unidentified calcium compartment. Homologous desensitization of NPY signalling might be explained by receptor-G protein uncoupling, while heterologous desensitization by BK could be the result of either transient depletion or inhibition of a mediator in the calcium signalling cascades activated by NPY.
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PMID:Neuropeptide Y Y2 receptor signalling mechanisms in the human glioblastoma cell line LN319. 1128 92

1. The modulation of 4-aminopyridine sensitive transient outward potassium current (4-AP I(to)) by neuropeptide Y (NPY) (100 nM) in rat ventricular myocytes was examined using the whole cell voltage-clamp technique. 2. Continuous exposure to NPY (100 nM) for 3 - 6 h significantly increased 4-AP I(to) density. The stimulation of 4-AP I(to) density by NPY was concentration-dependent (EC(50)=10 nM). 3. In the presence of BIBP 3226, an NPY receptor antagonist that binds selectively to NPY Y1-receptors, the effect of NPY on 4-AP I(to) density was maintained. However, in the presence of BIIE 0246, a highly selective non-peptide NPY Y2-receptor antagonist, NPY was unable to increase 4-AP I(to) density. 4. The effect of NPY on 4-AP I(to) density was prevented by pretreatment with 500 ng ml(-1) pertussis toxin (PTX) and by the specific protein kinase C (PKC) inhibitor, calphostin C (100 nM). 5. Thus, short term exposure to NPY induces an increase of 4-AP I(to) density in rat ventricular myocytes mediated by Y2-receptors and involving the action of PKC via a PTX-sensitive signalling cascade.
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PMID:Neuropeptide Y increases 4-aminopyridine-sensitive transient outward potassium current in rat ventricular myocytes. 1193 10

Neuropeptide Y (NPY) plays a modulatory role in processing nociceptive information. The present study investigated the effects of NPY on axonal transport of particles in neurites of cultured adult dorsal root ganglion (DRG) cells using video-enhanced microscopy. Application of NPY decreased the number of particles transported in both the anterograde and retrograde directions. This effect was persistently observed during NPY application and was reversed after washout. The inhibitory effect of NPY was concentration dependent between 10(-9) M and 10(-6) M. The instantaneous velocity of individual particles moving in anterograde and retrograde directions was also reduced by NPY. Both the NPY Y1 receptor agonist [Leu31,Pro34]-NPY and NPY Y2 receptor agonist NPY(13-36) mimicked the effect of NPY on the number of transported particles. An immunocytochemical study using an antiserum against the NPY Y1 receptor protein revealed that the Y1 receptor was expressed in the majority (85.9 %) of cultured adult mouse DRG cells. Pre-treatment of cells with pertussis toxin, a GTP-binding protein (G protein) inhibitor, completely blocked the inhibitory effect of NPY. Each application of SQ-22536, an adenylate cyclase inhibitor, and H-89, a protein kinase A inhibitor, mimicked and occluded the effect of NPY. In contrast, dibutyryl cAMP (dbcAMP), a membrane permeable cAMP analogue, and forskolin, an activator of adenylate cyclase, produced a transient increase in axonal transport. The application of dbcAMP and forskolin in combination with NPY negated the effect of NPY alone. These results suggest that NPY, acting at Y1 and Y2 receptors, inhibits axonal transport of particles in sensory neurones. The effect seems to be mediated by a pertussis toxin-sensitive G protein, adenylate cyclase, and protein kinase A pathway. Therefore, NPY may be a modulatory factor for axonal transport in sensory neurones.
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PMID:Neuropeptide Y inhibits axonal transport of particles in neurites of cultured adult mouse dorsal root ganglion cells. 1218 Dec 83


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