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)

In the human Ewing's sarcoma cell line WE-68, saturation analysis using 3H-labelled neuropeptide Y ([3H]NPY) as the radioligand disclosed a homogeneous population of binding sites with a dissociation constant (Kd) of 4.5 nM and maximal binding capacity (B(max)) of 712 fmol/mg cell protein. Besides the WE-68 cell line, ten other human Ewing's sarcoma cell lines (FM-62, HS-80, HT-78, HT-M1-78, NT-68, RM-82, RS-63, VH-64, WE-M1-68, WE-M2-68) were also found to display NPY receptors with Kd varying from 3.5 nM to 10.7 nM and B(max) = 247-3744 fmol/mg cell protein. NPY, its natural analogues and the Y1-receptor-specific peptide ligand [Leu31,Pro34]NPY inhibited [3H]NPY binding in the potency order: [Leu31,Pro34]NPY greater than or equal to human NPY greater than or equal to peptide YY (PYY) greater than salmon pancreatic polypeptide (PP) greater than human PP greater than porcine NPY13-36 much greater than NPY22-36. In the Ewing's sarcoma cell lines NPY provoked inhibition of forskolin-stimulated cyclic AMP formation by up to 98%. Pertussis toxin alleviated the cyclic-AMP-inhibitory response to NPY. In isolated Ewing's sarcoma plasma membranes pertussis toxin [32P]ADP-ribosylated a 41-kDa protein. The ability of NPY and analogues to inhibit cyclic AMP accumulation paralleled their potencies in displacing radioligand binding. By contrast, a cell line derived from an atypical form of Ewing's sarcoma did not express specific and functional NPY receptors. These results demonstrate that conventional Ewing's sarcoma cells possess Gi-protein-coupled NPY receptors of the Y1 type, which upon interaction with NPY, PYY, and PP mediate inhibition of cyclic AMP generation.
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PMID:Expression of functional Y1 receptors for neuropeptide Y in human Ewing's sarcoma cell lines. 132 Jun 24

Peptide YY (PYY), found in intestinal endocrine cells, and neuropeptide Y (NPY), a structural analogue of PYY found in neurons, inhibit gastric, pancreatic, and intestinal fluid and electrolyte secretion. We examined the effects of these peptides on dispersed chief cells from guinea pig stomach. PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion. These inhibitory peptides did not alter pepsinogen secretion caused by cholecystokinin, carbamylcholine, A23187, 8-bromo-cAMP, or a phorbol ester. The inhibitory effects of PYY on chief cell cAMP production occurred within 30 s, were independent of phosphodiesterase activity, and did not affect the actions of cholera toxin. However, the inhibitory effects of PYY were abolished when chief cells were preincubated with pertussis toxin, an agent that uncouples inhibitory guanine nucleotide binding (G) proteins from their receptors. In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP. PYY-induced attenuation of chief cell adenylate cyclase activity appears to involve activation of inhibitory G proteins.
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PMID:Actions of peptide YY and neuropeptide Y on chief cells from guinea pig stomach. 164 73

Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells.
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PMID:Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein. 210 80

The effect of islet-activating protein (IAP) purified from culture medium of Bordetella pertussis was examined in dogs. This was assessed by the levels of pancreatic polypeptide (PP) as well as the responses of plasma insulin and glucagon to a parasympathomimetic agent, bethanechol. Plasma responses of these pancreatic hormones were measured before and 5 days after IAP injection. Although IAP had no significant effect on the bethanechol-stimulated increase in plasma glucose, insulin and glucagon, the PP response to bethanechol was significantly reduced after IAP treatment compared with that before IAP (p less than 0.05). In conclusion, IAP significantly and selectively reduced bethanechol-stimulated PP release in the dog although the mechanism remained to be elucidated.
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PMID:Islet-activating protein (IAP) reduces bethanechol-stimulated release of pancreatic polypeptide in the dog. 675 97

1. We studied modulation of N-type Ca2+ channels in adult rat superior cervical ganglion (SCG) neurons by pancreatic polypeptide (PP) using whole cell clamp. In large (> 20 pF) SCG neurons, PP inhibited ICa (35 +/- 2%, mean +/- SE) in a concentration-dependent fashion, with one-half maximal inhibition at 19 nM. 2. One-third of the inhibition was blocked by pertussis toxin, about one-half was blocked by N-ethylmaleimide (NEM) treatments, and about one-half was voltage dependent. The NEM-insensitive component of the PP inhibition was voltage independent and not significantly blocked by intracellular Ca2+ chelators. 3. The NEM-insensitive component was only weakly attenuated by GDP-beta-S, and moderately reversible with guanosine 5'-triphosphate (GTP)-gamma-S, in the whole cell pipette, leaving open the possibility that it is not mediated by a G protein. 4. Hence, PP inhibits ICa via two mechanisms: one G-protein-mediated and the other possibly G-protein independent. The former pathway is sensitive to pertussis toxin (PTX) and NEM, voltage dependent, and shared by several other transmitters in these cells. The latter pathway is PTX-and NEM-insensitive, not voltage dependent, and not affected by the presence of intracellular Ca2+ chelators.
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PMID:Pancreatic polypeptide inhibits calcium channels in rat sympathetic neurons via two signaling pathways. 760 76

We examined the effects of neuropeptide Y (NPY) and pancreatic polypeptide on calcium currents (ICa) in acutely dissociated neurons from the adult rat superior cervical ganglion. We found that NPY inhibited the ICa with an estimated IC50 value of 140 nM. This inhibitory effect appeared to be restricted to a subset of cells which were smaller in diameter than the general population. The effect of NPY on the ICa was prevented by pretreatment with pertussis toxin, suggesting the involvement of a GTP-binding protein of the Gi or Go subtype. omega-conotoxin GVIA also occluded the effects of NPY, which suggests that these were directed toward N-type Ca++ channels. The effects of NPY were mimicked by the fragment NPY (13-36) but not by peptide YY, indicating that a receptor distinct from a Y1- or a Y2-like NPY receptor was involved. Finally, we also observed that pancreatic polypeptide inhibited the ICa, suggesting that a pancreatic polypeptide receptor is also present on superior cervical ganglion neurons.
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PMID:Neuropeptide Y and pancreatic polypeptide reduce calcium currents in acutely dissociated neurons from adult rat superior cervical ganglia. 809 66

Receptors for peptide YY (PYY) were identified in the PKSV-PCT renal proximal tubule cell line, derived from transgenic mice (SV40 large T antigen under the control of the rat L-type pyruvate kinase 5'-regulatory sequence). Binding of [125I-Tyr36]monoiodo-PYY ([125I] PYY to cell was specific, saturable, and reversible. The order of potency for peptides for inhibiting [125I]PYY binding was: PYY > neuropeptide Y (NPY) = PYY (13-36) >> pancreatic polypeptide. A single class of receptors was observed with a Kd of 0.37 +/- 0.05 nM and a Bmax of 103 +/- 10 fmol/mg protein. After cross-linking, electrophoresis of covalent [125I]PYY-receptor complexes revealed a single band of M(r) 50,000. PYY receptors were exclusively present at the basolateral membrane surface of polarized cells and were coupled negatively to adenylylcyclase by a pertussis toxin-sensitive G protein. PKSV-PCT cell growth and T antigen expression could be modulated by D-glucose in the medium. PYY receptors were exclusively expressed in proliferative cells cultured in the presence of D-glucose. PYY receptors disappeared in the absence of D-glucose and were expressed again when proliferation was activated by reintroduction of D-glucose. PYY stimulated cell growth (17-26% increase) and promoted [methyl-3H]thymidine incorporation into DNA (64% increase; ED50 = 5 nM PYY) of cells grown in D-glucose-enriched medium. This latter effect of PYY was largely reversed by pretreatment of cells with pertussis toxin. These findings suggest that PYY receptors play a role in epithelial cell growth.
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PMID:Peptide YY receptors in the proximal tubule PKSV-PCT cell line derived from transgenic mice. Relation with cell growth. 839 9

Neuropeptide Y (NPY) stimulated DNA synthesis in porcine aortic smooth muscle cells in a concentration-dependent manner. [Leu31, Pro34]NPY, a Y1-specific agonist, was several hundred times more potent than NPY(13-36), which preferentially bound to Y2 receptors, for stimulating DNA synthesis. On the other hand, human pancreatic polypeptide had no effect. The potency of NPY and related peptides for stimulating DNA synthesis paralleled their potency for increasing the cytosolic free Ca2+ concentration in the cells. Pertussis toxin treatment completely blocked both effects of the peptides. Thus, NPY may induce Ca2+ mobilization and stimulation of DNA synthesis in vascular smooth muscle cells via Y1 receptors whose signal transduction system involves pertussis toxin-sensitive GTP-binding protein(s).
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PMID:Neuropeptide Y stimulates DNA synthesis in vascular smooth muscle cells. 846 73

Whole-cell Ca2+ channel currents were recorded in human neuroblastoma (SH-SY5Y) cells, using conventional and perforated-patch techniques. Neuropeptide Y (NPY, 10-1000 nM) caused concentration-dependent inhibition of Ca2+ channel current amplitudes which was pertussis toxin-sensitive, voltage-dependent and associated with slowing of channel activation kinetics, regardless of which recording configuration was used. Inhibition was observed in all cells tested. Similar current inhibitions were observed with NPY (18-36) and peptide YY, but not with [Leu31, Pro34]NPY, indicating that the effects were mediated by Y2 receptors. Pancreatic polypeptide (100 nM) was without effect on Ca2+ channel currents. The effects of NPY were additive with nifedipine (at a supramaximal concentration of 5 microM), suggesting that NPY predominantly inhibits N-type Ca2+ channels present in these cells, and not L-type. The effects of NPY were mimicked by a novel, cyclic analogue of NPY which is 40-fold more selective for Y2 receptors than other commonly used Y2-selective peptides. The cyclic analogue was also more potent than NPY itself, causing maximal current inhibition at approx 300 nM, whereas the response to NPY was not fully saturated at 1 microM. Our results indicate that SH-SY5Y cells represent an excellent model system for studying the coupling of Y2 receptors to N-type channel inhibition. Furthermore, in the absence of selective antagonists for NPY receptor subtypes, the highly selective Y2 agonist cyclic NPY derivative may prove a useful tool for probing the various roles of Y2 receptors in the nervous system.
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PMID:Inhibition of Ca2+ channel currents in human neuroblastoma (SH-SY5Y) cells by neuropeptide Y and a novel cyclic neuropeptide Y analogue. 860 97

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


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