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)

Several regulatory peptides, including neuropeptide Y, can release histamine from mast cells. In the present study we investigated which parts of the neuropeptide Y molecule are required to evoke the release of histamine from isolated rat peritoneal mast cells. In addition, we examined whether the histamine release evoked by neuropeptide Y (and by compound 48/80) is sensitive to the G protein inhibitors pertussis toxin and benzalkonium chloride. Neuropeptide Y released histamine in a concentration-dependent manner. Also a neuropeptide Y analog with the center part substituted by 8-aminooctanoic acid, [Aoc2-27]neuropeptide Y, and the cyclic form of the C-terminal hexapeptide, cyclic neuropeptide Y-(31-36), released histamine. The three peptides were equally effective and equally potent. Neuropeptide Y-(1-24)NH2 also released histamine, but its efficacy was low. The rank order of potency of the analogs tested did not agree with that of any of the previously known or postulated neuropeptide Y receptors. Pretreatment of mast cells with pertussis toxin or benzalkonium chloride markedly inhibited the histamine release evoked by neuropeptide Y, [Aoc2-27]neuropeptide Y and compound 48/80. In conclusion, most of the histamine-releasing activity of neuropeptide Y resides in the six C-terminal amino acid residues. The release appears to be G protein-dependent and is probably not receptor mediated.
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PMID:Neuropeptide Y and truncated neuropeptide Y analogs evoke histamine release from rat peritoneal mast cells. A direct effect on G proteins? 752 49

Recent evidence suggests that peptides induce the release of mediators from rat peritoneal mast cell by means of a receptor-independent mechanism, possibly involving an interaction with sialic acid residues at the cell surface followed by the activation of a guanine nucleotide binding protein (G protein). We have now examined the potential involvement of sialic acid residues and of G protein stimulation in the activation of both human and rat cutaneous mast cells by neuropeptide Y, its C-terminal fragments and the wasp venom peptide, mastoparan. Neuropeptide Y-(18-36) was the most effective histamine releaser of the fragments tested, the order of potency being neuropeptide Y-(18-36) > neuropeptide Y-(22-36) > neuropeptide Y-(1-36). This order of potency suggests that the effects of the peptides are not mediated through classical NPY receptors. The hydrolysis of sialic acid residues by neuraminidase and the inhibition of G proteins by benzalkonium chloride or pertussis toxin significantly inhibited the secretory response of cutaneous mast cells to neuropeptide Y-(18-36) and mastoparan. These results demonstrate that the peptidergic pathway described for the activation of peritoneal rat mast cells is also involved in the response of cutaneous human and rat mast cells to peptides.
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PMID:Human and rat cutaneous mast cells: involvement of a G protein in the response to peptidergic stimuli. 753 61

Incubation of neuropeptide Y or its C-terminal fragments with rat peritoneal mast cells resulted in a dose-dependent histamine release. Fragment 18-36 of neuropeptide Y was the most biologically active peptide. EC25 value on rat mast cells was 7.2 +/- 2.2 nM. Neuropeptide Y was also able to induce a flare response after intradermal injection in humans. The histamine releasing effects of neuropeptide Y related peptides were greatly inhibited by pretreatment of rat mast cells with pertussis toxin or benzalkonium chloride. Neuropeptide Y and C-terminal related peptides also stimulated the GTPase activity of purified heterotrimeric G proteins in a dose-dependent manner from 1 to 50 microM. Binding studies with [125I]neuropeptide Y were unable to provide evidence for the presence of specific binding sites on the surface of mast cells. The alpha helical conformation of neuropeptide Y fragments was studied by measuring the circular dichroism spectra. Neuropeptide Y-(18-36) was the smallest fragment having a strong helical conformation. Our results demonstrate that neuropeptide Y activates mast cells through a non-specific process leading to G protein activation.
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PMID:Structural requirements for neuropeptide Y in mast cell and G protein activation. 754 Jan 43

Neuropeptide Y (NPY) is a widely distributed peptide with varied activities including inhibition of [3H]NE secretion from chromaffin cells. In the present study, we investigated the mechanism through which NPY and NPY fragments inhibit nicotinic receptor induced influx of 22Na+ and 45Ca++ into bovine chromaffin cells. Fragments of NPY, including NPY13-36, NPY18-36 and NPY26-36, are more potent inhibitors of 45Ca++ and 22Na+ influx than NPY. High [K+]- and BAY K 8644-induced 45Ca++ influx and veratridine-induced 22Na+ influx are not inhibited by either NPY or NPY fragments. Thus, the site of NPY or NPY fragment action is not voltage-gated Ca++ or Na+ channels. A significant amount of acetylcholine-induced 45Ca++ influx still occurs in the presence of the voltage-gated Ca++ channel blockers: nifedipine (L-type), omega-conotoxin-GVIA (N-type) and omega-agatoxin-IVA (P-type). NPY18-36, in the presence of these channel blockers, inhibited the residual nicotinic receptor-induced Ca++ influx. The response to NPY 18-36 is not pertussis toxin sensitive. The rank orders of potency for inhibition of 45Ca++ and 22Na+ are the same: NPY18-36 > or = NPY26-36 > NPY13-36 > NPY13-36 > NPY > or = NPYfree acid. Moreover, the IC50 values for NPY18-36 inhibition of 45Ca++ influx and 22Na+ influx are similar, 0.9 x 10(-6) M and 2.03 x 10(-6) M, respectively. Regression analysis for inhibition of these two phenomena produced a correlation coefficient of .9697 (P < .0003).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y (18-36) modulates chromaffin cell catecholamine secretion by blocking the nicotinic receptor ion channel. 754 75

Neuropeptide Y (NPY) and norepinephrine, found colocalized in sympathetic neurons innervating blood vessels, exert synergistic responses on vasoconstriction. To examine the signaling mechanisms involved, free of complications associated with mixed receptor populations, we have established a stable Chinese hamster ovary cell line expressing both Y1-NPY and alpha 1b-adrenergic receptors. Occupation of either receptor species, with 100 nM peptide YY (PYY) or 10 microM phenylephrine (PE), respectively, resulted in a rapid increase in the cytoplasmic free calcium concentration ([Ca2+]i) as assessed with Fura-2/AM. The rise due to PYY, but not that due to PE, was abolished by pretreatment with pertussis toxin. Both responses were largely maintained in the absence of extracellular Ca2+, but abolished by prior depletion of intracellular Ca2+ pools with either thapsigargin or 2,5-di-(t-butyl)-1,4-benzohydroquinone. Using cells prelabeled with myo-[3H]inositol, PE promoted a rapid (5 s) rise in inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) as analyzed by anion-exchange high pressure liquid chromatography, whereas the response to PYY (first significant at > 15 s post-stimulation) was too slow to play a causative role in Ca2+ mobilization. Combination of PE and PYY resulted in increases in [Ca2+]i which were at best additive, whereas they promoted a clearly synergistic rise in Ins(1,4,5)P3 at both 15 and 60 s. Co-stimulation also resulted in a synergistic activation of both protein kinase C (PKC) and [3H]arachidonic acid release. In either instance PYY alone was without effect. The potentiation of arachidonic acid release was abolished by depletion of cellular PKC following chronic treatment with phorbol esters. It is suggested that the ability of PYY to mobilize Ca2+ in an Ins(1,4,5)P3-independent fashion minimizes the functional importance of the capacity to potentiate PE-stimulated Ins(1,4,5)P3 generation. Instead the major consequences of the synergistic activation of phospholipase C are mediated via PKC, the other route of the signaling pathway.
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PMID:Synergistic interaction of Y1-neuropeptide Y and alpha 1b-adrenergic receptors in the regulation of phospholipase C, protein kinase C, and arachidonic acid production. 774 27

Neuropeptide Y (NPY) content, NPY receptors, and alpha-subunits of the G proteins Go and Gi were determined in cerebral cortex of male normotensive Wistar-Kyoto and spontaneously hypertensive rats at 3-28 wk of age and of adult female rats. NPY lacked major effects on adenylate cyclase or inositol phosphate formation. NPY content was similar in all normotensive groups but lower in spontaneously hypertensive rats at all ages. 125I-NPY labeled a homogeneous population of Y1-like receptors. The Y1 NPY receptor number gradually increased with age with similar values in both strains but was significantly smaller in female than in male rats. The Y1 NPY receptor affinity was similar in all male groups but greater in female rats. The abundance of immunodetectable Go alpha and Gi alpha and of pertussis toxin substrates was less at 3 wk than in older rats but similar in both sexes and strains. We conclude that rat cerebral cortex contains Y1-like receptors; sex, age, and blood pressure differentially regulate NPY content, Y1 NPY receptors, and Go alpha and Gi alpha.
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PMID:Regulation of NPY/NPY Y1 receptor/G protein system in rat brain cortex. 784 Mar 20

1. Melanostatin, a thirty-six amino acid peptide recently isolated from the frog brain due to its ability to inhibit alpha-melanocyte-stimulating hormone (alpha-MSH) release, is the amphibian counterpart of mammalian neuropeptide Y (NPY). The effect of synthetic melanostatin on the bioelectrical activity of cultured frog melanotrophs was studied in 124 cells by using the whole-cell patch-clamp technique. 2. In current-clamp experiments, melanostatin (1 microM) provoked a reversible hyperpolarization and a suppression of spontaneous action potentials. In some cells the hyperpolarizing response was absent, but an arrest of spike firing still occurred. 3. Melanostatin-induced hyperpolarization was associated with a decrease in membrane resistance. In voltage-clamp experiments, melanostatin induced an outward current at a constant command potential. This hyperpolarizing outward current appeared to be carried by potassium ions. 4. Cell dialysis with the non-hydrolysable GTP analogue guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) sustained the outward current produced by melanostatin. Dopamine (1 microM), which generates a similar hyperpolarizing outward current in frog melanotrophs, was not capable of increasing the current provoked by melanostatin and sustained by GTP gamma S. 5. Melanostatin also modulated voltage-operated currents. The amplitude of voltage-activated potassium current was increased by 30%. 6. Melanostatin reduced the fast sodium current. This inhibitory effect was rather persistent compared to the other modulated currents. 7. Melanostatin markedly scaled down high voltage-activated N- and L-like calcium currents. The activation kinetics of these two calcium currents were not altered by the peptide. 8. Pretreatment of melanotrophs with pertussis toxin (1 microgram ml-1) blocked melanostatin-induced inhibition of N- and L-like calcium currents. 9. It is concluded that the NPY-related peptide melanostatin generates a very complex pattern of electrical responses in frog melanotrophs, including hyperpolarization and modulation of voltage-activated currents underlying action potentials. G proteins appear to mediate at least part of these effects.
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PMID:Melanostatin (NPY) inhibited electrical activity in frog melanotrophs through modulation of K+, Na+ and Ca2+ currents. 791 31

Neuropeptide Y (NPY), a widely distributed peptide with varied activities, inhibits nicotinic receptor-induced [3H]norepinephrine ([3H]NE) secretion from bovine chromaffin cells. The secretion produced by membrane depolarization with high KCl concentrations or veratridine is not inhibited. Fragments of NPY, such as NPY18-36, are potent inhibitors of [3H]NE secretion, whereas [Leu31,Pro34]-NPY and peptide YY have no effect. The response to NPY18-36 is not sensitive to pertussis toxin pretreatment of chromaffin cells. NPY fragments also inhibit nicotinic receptor-induced 45Ca++ influx but not that induced by KCl or veratridine. The rank orders of potency for inhibition of [3H]NE secretion and 45Ca++ influx are the same: NPY18-36 > or = NPY26-36 > NPY13-36. NPY and NPYfree acid are weak inhibitors of secretion but not 45Ca++ influx. Moreover, the IC50s for NPY18-36 inhibition of [3H]NE secretion and 45Ca++ influx are comparable, 1.4 x 10(-6) M and 0.9 x 10(-6) M, respectively. Regression analysis produced a correlation coefficient of 0.9842 (P < .0001). It was concluded that NPY inhibits [3H]NE secretion by a modification of the nicotinic receptor-mediated increase in Ca++ influx. The characterization of the response suggests that the NPY effect is mediated by a previously undefined NPY receptor subtype that was designated Y4.
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PMID:Neuropeptide Y inhibition of nicotinic receptor-mediated chromaffin cell secretion. 796 58

Neuropeptide Y (NPY), a peptide present in the prostate gland, was found to inhibit vasoactive intestinal peptide (VIP)-stimulated cyclic AMP accumulation in isolated rat prostatic epithelial cells as well as VIP-stimulated adenylyl cyclase activity in rat prostatic membranes. The inhibitory effect of NPY was selective for the VIP receptor/effector system since it was also observed when using pituitary adenylyl cyclase activating peptide (PACAP-27) which presumably recognizes VIP receptors in this gland, but not when using unrelated substances such as isoproterenol or forskolin. NPY did not modify either the general lipid membrane microviscosity or the VIP-receptor binding. The inhibitory effect of VIP was blocked by pretreatment of the prostatic membranes with pertussis toxin. These results suggest the presence of NPY receptors in rat ventral prostate coupled in an inhibitory manner to adenylyl cyclase through a guanine nucleotide regulatory Gi protein.
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PMID:Neuropeptide Y inhibits vasoactive intestinal peptide-stimulated adenylyl cyclase in rat ventral prostate. 796 18

Neuropeptide Y (NPY) attenuated angiotensin II (AII)-or bradykinin (BK)-induced Ca2+ release from intracellular stores and inhibited forskolin-stimulated cAMP accumulation and omega-conotoxin-sensitive high K(+)-induced Ca2+ influx in the human neuroblastoma cell line SMS-KAN. All three NPY actions were mediated via Y2 receptors. Pretreatment with pertussis toxin completely abolished all of the NPY actions. Activation or down-regulation of protein kinase C had no effect on any NPY-mediated effect; herbimycin A, a tyrosine kinase inhibitor, only abolished the inhibitory effect of NPY on AII- or BK-induced Ca2+ mobilization. Herbimycin A also blocked platelet-derived growth factor-induced Ca2+ mobilization, which involves tyrosine kinase activation, and there was a good correlation in the concentration dependency between the two effects of herbimycin A, strongly suggesting that its ability to cancel the NPY effect is due to inhibition of tyrosine kinase activity. NPY attenuated AII- or BK-induced inositol 1,4,5-trisphosphate production, and herbimycin A reversed this NPY effect. These results provide the first evidence that Y2 receptors negatively couple to AII- or BK-induced phosphoinositide turnover leading to Ca2+ mobilization through pertussis toxin-sensitive GTP-binding protein(s). Inhibition of phospholipase C-beta activity by NPY seems to be mediated by activation of protein-tyrosine kinase or phosphotyrosine-containing protein(s).
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PMID:Y2 receptors for neuropeptide Y are coupled to three intracellular signal transduction pathways in a human neuroblastoma cell line. 813 19


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