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)

Neuropeptide Y (NPY) is released from an extensive network of postganglionic sympathetic perivascular neurons. NPY has been shown to affect vascular tone postsynaptically by 1) directly stimulating contraction; 2) inhibiting vasorelaxation; and 3) potentiating contraction elicited by exogenous vasoconstrictors. The molecular mechanisms mediating these effects of NPY are undefined. Therefore, we examined the possibility that NPY could stimulate smooth muscle contraction through myosin light chain phosphorylation in cultured porcine aortic smooth muscle cells. NPY (100 nM) caused a rapid, transient increase in myosin light chain (MLC) phosphorylation, an important regulatory event in the initiation of smooth muscle contraction. NPY-stimulated MLC phosphorylation was prevented by preincubation of cells with pertussis toxin and was independent of extracellular Ca2+. In parallel studies, NPY alone had no detectable effect on cellular cAMP or cGMP content; however, NPY potently inhibited forskolin-stimulated cAMP accumulation (IC50 = 0.03 nM) through a pertussis toxin-sensitive pathway. NPY had no detectable effect on basal phosphoinositide hydrolysis or protein kinase C activation but enhanced angiotensin II-stimulated production of inositol phosphates and activation of protein kinase C. These results indicate that NPY-stimulated MLC phosphorylation can occur in the absence of detectable changes in cAMP content, cGMP content, inositol phosphate production, or protein kinase C activation; however, the interactions between NPY and other vasoactive agents may be mediated by the indirect effects of NPY on adenylate cyclase activity and phosphoinositide hydrolysis.
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PMID:Neuropeptide Y stimulation of myosin light chain phosphorylation in cultured aortic smooth muscle cells. 217 Apr 10

Neuropeptide Y (NPY) inhibited the Ca2+ current (ICa) in rat dorsal root ganglion neurons in vitro. NPY inhibited the sustained ICa evoked by steps to 0 mV from a holding potential of -40 mV and the inactivating ICa, which was additionally evoked from a more negative holding potential of -80 mV. The effects of NPY on both phases of the ICa were abolished if cells were first treated with pertussis toxin (PTX). When a combination of GTP and the purified alpha-subunit of the guanine nucleotide-binding protein Go was perfused into PTX-treated cells, the inhibitory effects of NPY on the ICa reappeared in a time-dependent fashion. GTP or alpha-subunit perfused separately was relatively ineffective. The effects of NPY reappeared more rapidly at higher concentrations of alpha o. Chronic treatment of these cells with phorbol ester "down-regulates" protein kinase C (PKC) and reduces inhibition of the sustained current by NPY. In PTX-treated cells in which PKC had been removed by down-regulation, inhibition of ICa was also reconstituted following the perfusion of GTP/alpha o. Under these circumstances, NPY inhibited the transient phase of the ICa more than the sustained phase. These results indicate that Go, the major PTX substrate in the central nervous system, may normally mediate the inhibitory effects of NPY receptors on dorsal root ganglion Ca2+ channels.
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PMID:Guanine nucleotide-binding protein Go-induced coupling of neuropeptide Y receptors to Ca2+ channels in sensory neurons. 245 65

Neuropeptide Y (30-1000 nmol/l) significantly inhibited the fractional stimulation-induced outflow of radioactivity from mouse atria preincubated with [3H]-noradrenaline. The inhibitory effect of neuropeptide Y was observed at all frequencies tested (2, 5 and 10 Hz) as well as after alpha-adrenoceptor blockade with phentolamine (1 mumol/l). A combination of 8-bromo adenosine cyclic-3'-5'-monophosphate (90 or 270 mumol/l) with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (100 mumol/l) was used to saturate maximally the adenylate cyclase system and these drug combinations significantly enhanced the stimulation-induced outflow of radioactivity. However, neuropeptide Y inhibited the stimulation-induced outflow in the presence of these drugs, suggesting that the inhibitory effect of neuropeptide Y was not due to decreasing endogenous cyclic AMP formation. Finally, atria from mice treated with pertussis toxin were used. In this case, the inhibitory effect of neuropeptide Y on the stimulation-induced outflow of radioactivity was still observed suggesting that inhibitory prejunctional neuropeptide Y receptors are not coupled to a pertussis toxin-susceptible G protein.
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PMID:Inhibition of noradrenaline release by neuropeptide Y in mouse atria does not involve inhibition of adenylate cyclase or a pertussis toxin-susceptible G protein. 248 50

Neuropeptide Y (NPY) presynaptically inhibits excitatory transmission in area CA1 of rat hippocampus. As postsynaptic NPY receptors in certain other tissues have been shown to be coupled to G-proteins, we have tested the hypothesis that the hippocampal NPY effects are also mediated by G-proteins. Pretreatment of rats with pertussis toxin (PTX) was ineffective in blocking NPY's presynaptic inhibitory actions in area CA1 of the hippocampal slice. The presynaptic inhibitory action of baclofen was also unaffected by PTX pretreatment. However, in these same PTX-pretreated slices, the postsynaptic hyperpolarizing actions of baclofen and 5-hydroxytryptamine were blocked. We suggest that pre- and postsynaptic receptors possess different coupling mechanisms to their effectors.
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PMID:Presynaptic inhibition by neuropeptide Y and baclofen in hippocampus: insensitivity to pertussis toxin treatment. 250 90

Neuropeptide Y (NPY) is a unique 36-amino acid peptide found in high concentrations in brain and peripheral neurons. Although NPY is present in kidney tissue, its role in regulation of renal function has not been delineated. We found that NPY significantly decreases arginine vasopressin (AVP) but not adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated hydraulic conductivity (Lp) in perfused rat cortical collecting tubules (CCT). Either alpha 2-adrenergic receptor blockade (yohimbine) or occupancy (clonidine) prevent NPY inhibition of AVP-stimulated Lp. By contrast, alpha 1-adrenergic receptor blockade with prazosin did not alter NPY inhibition of AVP action. Pretreatment of CCT with pertussis toxin also abolishes NPY inhibition of AVP-stimulated Lp. These data suggest that NPY acts via an alpha 2-adrenergic receptor coupled to a pertussis toxin-sensitive protein to inhibit AVP-stimulated cAMP formation and Lp in the rat CCT.
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PMID:Mechanism of neuropeptide Y inhibition of vasopressin action in rat cortical collecting tubule. 253 78

Neuropeptide Y (NPY) regulation of intracellular cyclic AMP accumulation was studied in human Ewing's sarcoma cell line, WE-68. NPY inhibited vasoactive intestinal peptide (VIP)- and dopamine-stimulated but not basal cyclic AMP formation. The peptide effect was rapid (less than 2 min), concentration-dependent with a half-maximal effective concentration (EC50) of 8 nM NPY, and maximal inhibition reaching 60-70% with 100 nM NPY. Prior exposure of WE-68 cells to pertussis toxin completely abolished the inhibitory action of NPY. It is concluded that NPY attenuates agonist-stimulated cyclic AMP formation in Ewing's sarcoma WE-68 cells, and may do so via the inhibitory guanine nucleotide regulatory protein of adenylate cyclase.
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PMID:Neuropeptide Y inhibits vasoactive intestinal peptide- and dopamine-induced cyclic AMP formation in human Ewing's sarcoma WE-68 cells. 254 51

Neuropeptide Y (NPY) is the most powerful peptide drug stimulating feeding in rats. Rats with paraventricular hypothalamic (PVH) cannulae were used to investigate the mechanisms involved in NPY-induced feeding. Consistent with previous reports, injection of 2 micrograms of NPY into the PVH significantly increased the cumulative food intake over 1-, 2- and 4-hr periods. Ad lib feeding decreased significantly two days after pertussis toxin (PT) administration, but recovered to nearly normal levels on the fourth day. PT had no immediate effect on NPY-induced feeding; however, four days after PT was injected NPY (2 micrograms) did not increase the food intake compared to control. In vitro investigations showed that isoproterenol-stimulated adenylate cyclase activity in the hypothalamus of control rats was inhibited by NPY. In PT-treated rats, however, no inhibition of cAMP production was observed. These results suggest that cAMP may mediate NPY-induced feeding and that a PT-sensitive G protein may be involved in this signal transduction.
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PMID:Pertussis toxin inhibits neuropeptide Y-induced feeding in rats. 256 Jan 78

Neurotransmitter receptor coupling to adenylate cyclase (AC) was studied in the cultured human neuroblastoma SK-N-MC cell line. Activation of beta-adrenoceptors with isoprenaline (ISO) or vasoactive intestinal polypeptide (VIP) receptors, increased AC activity in a dose-dependent manner. Preincubation with ISO and VIP induced a ligand specific, i.e. homologous type of desensitization of the respective receptor. Neuropeptide tyrosine (NPY) was able to inhibit ISO as well as VIP induced AC activity. The effect of NPY was totally abolished in cells pretreated with pertussis toxin to inactivate inhibitory G-proteins. Thus, SK-N-MC cells possess functionally coupled beta-adrenoceptors, VIP and NPY receptors, and may be used to study interactions between ligands and receptors which couple to the AC system.
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PMID:Beta-adrenoceptor, vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY) receptors functionally coupled to adenylate cyclase in the human neuroblastoma SK-N-MC cell line. 283 76

Neuropeptide Y, a major neuropeptide and potent vasoconstrictor, inhibited isoproterenol-stimulated adenylate cyclase activity in cultured rat atrial cells as well as in atrial membranes. Prior treatment of the cells with pertussis toxin blocked the inhibitory action of neuropeptide Y. Pertussis toxin is known to uncouple the receptors for other inhibitors of adenylate cyclase by ADP-ribosylation of the alpha-subunit of Gi, the inhibitory guanine nucleotide binding component of adenylate cyclase. The toxin specifically catalyzed the ADP-ribosylation of a 41-kilodalton atrial membrane protein which corresponded to the Gi subunit. These results suggest that neuropeptide Y may mediate some of its physiological effects through specific receptors linked to the inhibitory pathway of adenylate cyclase.
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PMID:Neuropeptide Y inhibits cardiac adenylate cyclase through a pertussis toxin-sensitive G protein. 302 13

Neuropeptide Y (NPY), a peptide often coreleased with catecholamines, appears to be an important component of the sympathetic nervous system, but little is known about the molecular basis of its action. We introduce here human erythroleukemia (HEL) cells as a new model system for studies of NPY action. NPY inhibited adenosine 3,5'-cyclic monophosphate (cAMP) accumulation in HEL cells with a 50% effective concentration (EC50) of 3 nM. Additionally NPY increased intracellular Ca2+, as assessed by fura-2 fluorescence, with a similar EC50. Pretreatment with pertussis toxin blocked both responses, suggesting the involvement of one or more G proteins. Chelating extracellular Ca2+ with EGTA did not reduce the Ca2+ signal, demonstrating mobilization from intracellular stores rather than influx. Experiments with various agents demonstrated that the Ca2+ mobilization was not secondary to lowering of cAMP levels, formation of arachidonic acid products, or Na+-H+ exchange. Ca2+ mobilization also did not appear to be associated with inositol phosphate generation. In conclusion, we demonstrate for the first time that NPY, in addition to inhibiting adenylate cyclase, also can elevate intracellular Ca2+. HEL cells should prove useful in further studies of the molecular basis of NPY action.
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PMID:Neuropeptide Y mobilizes Ca2+ and inhibits adenylate cyclase in human erythroleukemia cells. 320 64


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