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 PC-12 cells differentiated with nerve growth factor, neuropeptide Y (NPY) potentiated the K(+)-evoked increase in intracellular calcium, but this potentiation was not mediated by classical Y1 or Y2 NPY receptors. The potentiation by NPY appeared to occur through the mobilization of calcium from intracellular stores because thapsigargin successfully blocked the potentiation. In contrast, the Y2 agonist, NPY-(13-36), attenuated the K(+)-evoked increase in intracellular calcium by decreasing the influx of extracellular calcium. The effect of NPY-(13-36) on dopamine release from PC-12 cells was next studied. NPY-(13-36) significantly attenuated the K(+)-evoked dopamine release in a concentration-dependent manner. Nifedipine and omega-conotoxin also attenuated the evoked dopamine release. In the presence of nifedipine or omega-conotoxin, NPY-(13-36) produced further inhibition of the evoked dopamine release. Furthermore, NPY-(13-36)-induced inhibition of dopamine release was abolished by pertussis toxin pretreatment. We conclude that the regulatory effects of NPY and analogues on intracellular calcium are mediated by multiple NPY receptor subtypes. Y2 receptor-mediated pertussis toxin-sensitive inhibition of the evoked dopamine release does not seem to be due to interactions with L- or N-type Ca2+ channels.
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PMID:Modulation of intracellular calcium transients and dopamine release by neuropeptide Y in PC-12 cells. 816 42

Neuropeptide Y is colocalized with noradrenaline in sympathetic fibers innervating the rat pineal gland. In this article we present a study of the effects and mechanisms of action of neuropeptide Y on the pineal noradrenergic transmission, the main input leading to the rhythmic secretion of melatonin. At the presynaptic level, neuropeptide Y inhibits by 45%, with an EC50 of 50 nM, the potassium-evoked noradrenaline release from pineal nerve endings. This neuropeptide Y inhibition occurs via the activation of pertussis toxin-sensitive G protein-coupled neuropeptide Y-Y2 receptors and is independent from, but additive to, the alpha 2-adrenergic inhibition of noradrenaline release. At the postsynaptic level, neuropeptide Y decreases by a maximum of 35%, with an EC50 of 5 nM, the beta-adrenergic induction of cyclic AMP elevation via the activation of neuropeptide Y-Y1 receptors. This moderate neuropeptide Y-induced inhibition of cyclic AMP accumulation, however, has no effect on the melatonin secretion induced by a beta-adrenergic stimulation. On the contrary, in the presence of 1 mM ascorbic acid, neuropeptide Y potentiates (up to threefold) the melatonin secretion. In conclusion, this study has demonstrated that neuropeptide Y modulates the noradrenergic transmission in the rat pineal gland at both presynaptic and postsynaptic levels, using different receptor subtypes and transduction pathways.
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PMID:Presynaptic and postsynaptic effects of neuropeptide Y in the rat pineal gland. 818 49

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

The effects of pertussis toxin on the intraocular pressure (IOP) lowering effect of clonidine and isoproterenol as well as on the inhibitory effects of clonidine and neuropeptide Y on adenylate cyclase activity of ciliary processes were studied in albino rabbits. I.v. administered pertussis toxin elicited transient changes in IOP which, however, returned to control values during 2-3 days. In the following days the IOP lowering effect of the alpha 2-adrenergic agonist clonidine was abolished and that of the nonselective beta-adrenergic agonist isoproterenol was attenuated. At the same time, the inhibitory effects of clonidine and neuropeptide Y on basal as well as stimulated adenylate cyclase activities in homogenates of ciliary processes were grossly diminished. The effects of pertussis toxin on the IOP lowering action of adrenergic agonists and on the inhibitory action of clonidine and neuropeptide Y on adenylate cyclase activity were ascribed to an impairment of the function of a G protein in ciliary processes, probably G(i) protein. It is suggested that the decrease of IOP induced by clonidine is due to inhibition of adenylate cyclase.
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PMID:Effects of pertussis toxin on intraocular pressure and adenylate cyclase activity of ciliary processes in rabbits. 840 17

Specific binding sites for neuropeptide Y could be demonstrated in primary cultures of astrocytes from neonatal rat brain. Neuropeptide Y binding was saturable, reversible, and temperature dependent as revealed by saturation studies and kinetic experiments. Scatchard analysis of equilibrium binding data indicated a single population of high-affinity binding sites with respective KD and Bmax values of 0.43 nM and 6.9 fmol/2.7 x 10(5) cells. Physiological responses induced by neuropeptide Y could be detected in a distinct subpopulation of cultured astrocytes on the basis of two criteria: 1) electrophysiological responses and 2) single cell measurements of changes in [Ca2+]i. In that fraction of cells responding (20-70%, varying among cultures from different preparations), brief application of neuropeptide Y led to a membrane potential depolarization, lasting several minutes. When the membrane was clamped close to the resting membrane potential using the whole-cell patch-clamp technique, neuropeptide Y induced an inward current with a similar time course as the neuropeptide Y-induced membrane depolarization. As detected by single cell microfluorimetric (fura-2) measurements neuropeptide Y induced an increase of [Ca2+]i which was caused by the entry of extracellular Ca2+. Both the [Ca2+]i increase and the electrophysiological responses were unaffected by pretreatment of the astrocytes with pertussis toxin.
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PMID:Identification of neuropeptide Y receptors in cultured astrocytes from neonatal rat brain. 845 May 63

Evidence is presented that the neuropeptide Y receptor is directly coupled to an inhibitory G protein existing in cultured bovine adrenal chromaffin cell membranes. Pertussis toxin catalyzes the [32P]ADP-ribosylation of a 41 kDa plasma membrane protein. 5'-Guanylylimidodiphosphate inhibited the [32P]ADP labelling of this protein in a dose-dependent manner whereas GTP had no effect. Preincubation of the plasma membranes with high concentrations of neuropeptide Y followed by a brief exposure to a low concentration of 5'-guanylylimidodiphosphate significantly inhibited ADP-ribosylation beyond that observed with 5'-guanylylimidodiphosphate alone. These results suggest that the neuropeptide Y receptor in bovine adrenal chromaffin cells is directly coupled to a 41 kDa PTX substrate (presumably the alpha subunit of an inhibitory G protein).
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PMID:Neuropeptide Y inhibits pertussis toxin-catalyzed ADP-ribosylation in bovine adrenal chromaffin cell membranes. 850 26

This study investigated the type of G-protein alpha subunit(s) that human neuropeptide Y (NPY)1 receptors preferentially utilize when activating G-protein gated K+ currents. Two electrode voltage-clamp recordings were made from Xenopus oocytes that had been injected with cDNAs encoding either human NPY1 or D2(short) dopamine receptors, and GIRK1 a cloned rat brain K+ channel. These receptors were also co-injected with G-protein alpha i1, alpha i2, alpha i3 and alpha o1 subunits to determine which subunit(s) modulate the efficiency of signal transduction. In NPY1 receptor injected cells neuropeptide Y (100 nM) caused a 53 +/- 10 nA inward current (n = 14; EC50 = 3 nM) and this effect was blocked by pertussis toxin (500 ng ml-1 24 h). Activation of GIRK1 currents by neuropeptide Y was selectively potentiated by alpha i1 subunit cDNA whereas coupling dopamine of D2 receptors to this channel was not.
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PMID:Involvement of G-protein alpha il subunits in activation of G-protein gated inward rectifying K+ channels (GIRK1) by human NPY1 receptors. 858 Dec 66

The proteolytic cleavage product of complement component 3, (C3a), is like C4a and C5a, is a potent anaphylatoxin and induces the production of inflammatory mediators in phagocytes. Notably, mast cells respond to C3a with the release of vasoactive substances, including histamine. We have examined the function and receptor binding of C3a in a human leukemic mast cell line, HMC-1. Similar to chemoattractant agonists in leukocytes, C3a induced rapid cytosolic free calcium concentration increases in HMC-1 cells. EGTA did not diminish this response, indicating that mobilizable Ca2+ was from intracellular stores. Receptors of C3a in HMC-1 cells couple in part to Bordetella pertussis toxin-sensitive G-proteins and, therefore, appear to belong to the family of serpentine receptors that require G-proteins for signal transduction. HMC-1 cells express two types of C3a receptors, C3aR1 and C3aR2, that were shown to bind 125I-C3a with high-(Kd1 = 2.1-4.8 nM) or low-affinity (Kd2 = 30-150 nM), and both receptors are expressed at high level: 3 x 10(5)-6 x 10(5) C3aR1/cell and 5 x 10(5)-2.3 x 10(6) C3aR2/cell. Results from cross-linking experiments with 125I-C3a fully agree with the presence of two different classes of C3a receptors in HMC-1 cells. Two membrane proteins with apparent molecular masses of 54-61 kDa (p57) and 86-107 kDa (p97) could be covalently modified with 125I-C3a, and this cross-linking was inhibited with an excess of unlabeled C3a. Many of the known agonists for leukocytes including 13 chemokines (IL-8, NAP-2, GRO alpha, ENA-78, IP10, PF4, MCP-1, 2 and 3, RANTES, MIP-1 alpha, MIP-1 beta and I309), three neuropeptides (neuropeptide Y, somatostatin and calcitonin), as well as C5a, did not activate HMC-1 cells, indicating that C3a is one of a few protein ligands for which this cell line expresses specific receptors. The apparent selectivity for C3a and the abundant expression of C3a receptors make the HMC-1 cell line an excellent choice for the cloning of the receptor genes.
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PMID:Expression of high- and low-affinity receptors for C3a on the human mast cell line, HMC-1. 862 64

In contrast to its inhibitory role in mature neurons, GABA can exert excitatory actions in developing neurons, including mediation of increases in cytosolic Ca2+. Modulation of this excitatory activity has not been studied previously. We used Ca2+ digital imaging with Fura-2 to test the hypothesis that neuropeptide Y (NPY) would depress GABA-mediated Ca2+ rises in neurons cultured from the developing suprachiasmatic nucleus (SCN). SCN neurons were chosen as a model system for this study because SCN neurons are primarily GABAergic, they express high levels of NPY and GABA receptors, and functionally, NPY causes profound phase-shifts in SCN-generated circadian rhythms. Vigorous GABA-mediated Ca2+ activity was found in young SCN neurons that were maintained in vitro for 4-14 d. NPY showed a dose-dependent rapid depression of the amplitude of Ca2+ rises generated by GABA released from presynaptic SCN axons. NPY exerted a long-term depression of cytosolic CA2+ in the majority of neurons tested, which lasted more than 1 hr after NPY washout. The magnitude of the NPY depression was dose-dependent. NPY did not affect Ca2+ levels when GABAA receptor activity was blocked by bicuculline; however, when bicuculline and NPY were withdrawn from the perfusion solution, the subsequent CA2+ rise was either significantly reduced or completely absent, suggesting that the NPY receptor was activated in the absence of elevated intracellular Ca2+ and GABAA receptor activity, and that the latent effect of NPY was revealed only after depolarizing GABA stimulation was renewed. Pretreating neurons with pertussis toxin greatly reduced the ability of NPY to depress GABAergic Ca2+ rises, suggesting that the NPY modulation of the GABA activity was based largely on a mechanism involving pertussis toxin-sensitive Gi/Go proteins. NPY receptor stimulation depressed (< 30%) postsynaptic Ca2+ rises evoked by GABA (20 microM) application in the presence of tetrodotoxin (TTX). The effects of NPY were mimicked by the NPY Y1 receptor agonist [Pro34,Leu31] NPY and the Y2 receptor agonist NPY 13-36 and by peptide YY (PYY). Together, our data suggest that the Y1 and Y2 type NPY receptors act both presynaptically and postsynaptically to depress GABA-mediated Ca2+ rises. If related mechanisms exist in peptide modulation of inhibitory GABA activity in mature neurons, this could underlie long-term changes in the behavior of neurons of the SCN necessary for phase-shifting the circadian clock by NPY, NPY also modulated GABA responses in neuroendocrine neurons from the hypothalamic arcuate nucleus. NPY thus can play an important role in evoking long-term depression of GABA-mediated Ca2+ activity in these developing neurons, allowing NPY-secreting cells to modulate the effects of GABA on neurite outgrowth, gene expression, and physiological stimulation. This is the first example of such a cellular memory: that is, long-term Ca2+ depression based on modulation of depolarizing GABA activity.
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PMID:Neuropeptide Y depresses GABA-mediated calcium transients in developing suprachiasmatic nucleus neurons: a novel form of calcium long-term depression. 862 85

This study was performed in order to test the hypothesis that the connecting peptide of proinsulin, C-peptide, might in itself possess biological activity. Renal tubular Na+, K(+)-ATPase, which is a well-established target for many peptide hormones, was chosen as a model. Rat C-peptide (I) was found to stimulate Na+, K(+)-ATPase activity in single, proximal convoluted tubules dissected from rat kidneys. C-peptide increased the Na+ affinity of the enzyme and all subsequent studies were performed at non-saturating Na+ concentrations. C-peptide stimulation of Na+, K(+)-ATPase activity occurred in a concentration-dependent manner in the dose range 10(-8)-10(-6) mol/l. The presence of neuropeptide Y, 5 x 10(-9) mol/l, enhanced this effect and stimulation of Na+, K(+)-ATPase activity then occurred in the C-peptide dose range 10(-11)-10(-8) mol/l. C-peptide stimulation of Na+, K(+)-ATPase activity was abolished in tubules pretreated with pertussis toxin. It was also abolished in the presence of FK 506, a specific inhibitor of the Ca2(+)-calmodulin-dependent protein phosphatase 2B. These results indicate that C-peptide stimulates Na+, K(+)-ATPase activity, probably by activating a receptor coupled to a pertussis toxin-sensitive G-protein with subsequent activation of Ca2(+)-dependent intracellular signalling pathways.
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PMID:C-peptide stimulates rat renal tubular Na+, K(+)-ATPase activity in synergism with neuropeptide Y. 863 72


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