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)

Injection of rats with a single dose of epidermal growth factor (EGF) or isoproterenol increased parotid gland acinar cell levels of cyclic AMP (cAMP) significantly above control basal concentrations (34, 177 and 11.5 pmol/g tissue/100 g body weight, respectively). Following a chronic regimen of isoproterenol (3 days), EGF, bovine galactosyltransferase (Gal Tase, EC 2.4.1.22) and isoproterenol increased cAMP levels, albeit to a lower level than observed for the single dose (21, 17 and 51 pmol, respectively). Using isolated parotid gland membranes, EGF and bovine galactosyltransferase also stimulated adenylate cyclase (EC 2.7.4.3) activity in a concentration-dependent manner. Introduction of the beta-adrenergic receptor antagonist propranolol blocked isoproterenol-stimulated adenylate cyclase activity and cAMP accumulation, but not that observed with EGF or the transferase treatment. Growth factor-stimulated adenylate cyclase activity required the presence of the guanosine triphosphate (GTP) analogue, guanyl-5'-imidodiphosphate (p[NH]ppG), while cAMP accumulation could additionally be blocked by introducing the GDP analog, guanosine 5'[beta-thio]diphosphate (GDP[S]). The ability of EGF to activate adenylate cyclase was not affected by pretreatment of acinar cell membranes with pertussis toxin, whereas pretreatment with cholera toxin eliminated EGF-stimulated cyclase activity. The experimental results presented here expand to the parotid gland our knowledge of the ability of EGF to stimulate the cAMP second messenger signalling pathway via a G-binding regulatory protein, by a mechanism independent of beta-adrenergic receptor activation.
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PMID:Epidermal growth factor activation of rat parotid gland adenylate cyclase and mediation by a GTP-binding regulatory protein. 166 11

Human recombinant interleukin-2 and rat recombinant IL-2 microinjected into the locus coeruleus of rats, induced typical dose-dependent behavioural sedation and/or sleep and electrocortical synchronization. During sleep induced by this lymphokine a dose-dependent increase in total voltage power (0.25-16 Hz) as well as in the 0.25-3, 3-6 and 6-9 Hz frequency bands was observed. The behavioural and electrocortical effects of interleukin-2 were blocked in animals pretreated with anti-IL-2 monoclonal antibodies and with naloxone, whereas they were still evident in rats pretreated with yohimbine. In addition, the behavioural and electrocortical slow-wave sleep effects observed after the administration of interleukin-2 into the locus coeruleus were reduced significantly or antagonized completely by a previous pretreatment with pertussis toxin, forskolin, dibutyryl-cyclic-AMP and 8-bromo-cyclic-AMP. These results are consistent with the hypothesis that the behavioural and electrocortical changes of this lymphokine are mediated at locus coeruleus level via a guanine regulatory Gi protein coupling IL-2 specific receptors to the adenylate cyclase system.
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PMID:Effects of pertussis toxin, dibutyryl-cyclic-AMP, bromo-cyclic-AMP and forskolin on the behavioural and electrocortical power spectrum changes induced by microinfusion of interleukin-2 into the locus coeruleus. 166 94

Neurokinins are a family of neuropeptides with widespread distribution mediating a broad spectrum of physiological actions through three distinct receptor subtypes: NK-1, NK-2, and NK-3. We investigated some of the second messenger and cellular processes under control by the recombinant bovine NK-2 receptor stably expressed in Chinese hamster ovary cells. In this system the NK-2 receptor displays its expected pharmacological characteristics, and the physiological agonist neurokinin A stimulates several cellular responses. These include 1) transient inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization, 2) increased out put of arachidonic acid and prostaglandin E2 (PGE2), 3) enhanced cyclic AMP (cAMP) generation, 4) increased de novo DNA synthesis, and 5) an induction of the "immediate early" genes c-fos and c-jun. Although NK-2 receptor-mediated IP3 formation involves activation of a pertussis toxin-insensitive G-protein, increased cAMP production is largely a secondary response and can be at least partially attributed to autocrine stimulation by endogenously generated eicosanoids, particularly PGE2. This is the first demonstration that a single recombinant neurokinin receptor subtype can regulate, either directly or indirectly, multiple signal transduction pathways and suggests several potential important mediators of neurokinin actions under physiological conditions.
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PMID:Recombinant bovine neurokinin-2 receptor stably expressed in Chinese hamster ovary cells couples to multiple signal transduction pathways. 166 1

In the human T-cell line, Jurkat, the accumulation of cyclic AMP induced by adenosine is enhanced by tumor-promoting phorbol esters, whereas prostaglandin E2 receptor-stimulated cAMP accumulation is antagonized (Nordstedt et al. 1989). In the present study we examine the involvement of pertussis toxin sensitive guanine nucleotide binding proteins (G-proteins) in producing the phorbol ester effects. Pertussis toxin pretreatment of the Jurkat cells invariably caused an ADP ribosylation of two G-proteins that inhibit adenylyl cyclase, tentatively identified as Gi2 and Gi3, using Western blots. Pertussis toxin treatment had little effect on basal cAMP accumulation, but sometimes inhibited, sometimes stimulated agonist and cholera toxin induced cAMP accumulation. The latter effect was not mimicked by the B-oligomer. Irrespective of whether pertussis toxin stimulated or inhibited NECA and cholera toxin-induced cAMP accumulation it could not block the effect of phorbol-12,13-dibutyrate (PDBu). The inhibitory effect of PDBu on prostaglandin E2-induced cAMP accumulation was, however, invariably eliminated by pertussis toxin treatment. In conclusion, activation of protein kinase C by phorbol esters reveals a Gi-mediated prostaglandin E receptor-induced inhibition of adenylate cyclase in addition to the prostaglandin E receptor-mediated stimulation of cAMP accumulation in Jurkat cells. The enhancement of adenosine A2 receptor stimulated cAMP accumulation by PDBu, on the other hand, does not involve a PTX sensitive Gi-protein.
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PMID:Role of a pertussis toxin sensitive G-protein in mediating the effects of phorbol esters on receptor activated cyclic AMP accumulation in Jurkat cells. 166 31

We have previously reported that the response of cultured chick cerebellar neurons to glutamate is enhanced by noradrenaline (NA) or isoproterenol and suppressed by clonidine. The present study was carried out to further specify the adrenergic receptor subtypes involved in the facilitatory effect of NA or isoproterenol and the suppressive effect of clonidine, and to examine the intracellular mechanisms underlying these modulatory effects of NA. The clonidine effect, which was mimicked by NA iontophoresed with large ejecting currents, was blocked by yohimbine and tolazoline (alpha 2 antagonists) and also by dibutyryl cyclic AMP or forskolin which augmented the glutamate response by itself. Prazosin, an alpha 1 receptor antagonist did not block the clonidine effect. NA- or isoproterenol-induced facilitation, which was mimicked by denopamine (beta 1 agonist), was antagonized by acebutolol (beta 1 antagonist) and not by ICI 118,551 (beta 2 antagonist). Pretreatment of neurons with pertussis toxin for more than 24 h blocked the suppressive action of clonidine without affecting the facilitatory action of isoproterenol. Furthermore, intracellular injection of GDP beta S inhibited the modulatory effects of either clonidine or isoproterenol. These results indicate that the facilitatory and inhibitory modulatory effects of NA may be mediated by beta 1 and alpha 2 receptors linked to cAMP systems, respectively, and the former is coupled with the stimulatory G protein (Gs) and the latter is with the inhibitory G protein (Gi).
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PMID:Subtypes of adrenergic receptors and intracellular mechanisms involved in modulatory effects of noradrenaline on glutamate. 167 79

The characteristics of histamine H1-receptors expressed on astrocytes from the cerebral cortex of new born rats were analysed by the [3H]-mepyramine binding assay. The apparent dissociation constant (Kd) was 10.4 nM and the binding capacity (Bmax) of 262 fmol/mg protein. H1-antagonists inhibited the [3H]mepyramine bindings and the isomers of chlorpheniramine showed a stereoselectivity for the inhibition of the bindings. Two distinct populations of cultured astrocytes, type-1 and type-2 astrocytes, were enriched and histamine-induced accumulations of inositol phosphates (IP) and cyclic AMP and histamine-evoked Ca++ signals were examined. Histamine stimulated the accumulation of IP in type-2 astrocytes, but not in type-1 astrocytes. The accumulation of cyclic AMP induced by histamine was observed in type-1 astrocytes, although not in type-2 astrocytes. Histamine-induced Ca++ signals were observed in 17.2% of type-1 astrocytes and in 72.9% of type-2 astrocytes. Histamine-induced Ca++ signals in type-2 astrocytes were antagonized by H1-antagonists, but not by H2- antagonists. Histamine-induced Ca++ signals were classified into 4 patterns, ie. transient, oscillatory, sustained and biphasic. When extracellular Ca++ was omitted or La was added to the extracellular medium, sustained phase of Ca++ signal disappeared and transient and oscillatory patterns were only observed. Phorbol ester inhibited histamine-induced Ca++ signals but pertussis toxin (IAP) and organic voltage dependent Ca++ channel blockers had no effect. Histamine-induced Ca++ elevation appeared initially in processes and then Ca++ wave propagated to the cell soma. Ca++ elevation was observed only in the processes in some cells.
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PMID:Histamine H1-receptors on astrocytes in primary cultures: a possible target for histaminergic neurones. 167 32

In cerebellar granule cells, baclofen acted with micromolar concentrations at proposed gamma-aminobutyric acid-B receptors to inhibit the formation of cyclic AMP and depolarization-induced release of glutamate. Nanomolar concentrations of baclofen inhibited depolarization-induced influx of calcium. All three responses to baclofen were attenuated after pertussis toxin pretreatment of cell cultures. The inhibition of calcium influx and glutamate release were reversed by the cyclic AMP analog, 8-(4-chlorphenylthio)-cyclic AMP. The release of glutamate was dependent on the influx of extracellular calcium, which enters the cell through dihydropyridine-sensitive voltage-dependent calcium channels. Because the decrease in calcium influx by baclofen and nifedipine were additive, the baclofen-mediated decrease in calcium influx may not involve a dihydropyridine-sensitive calcium channel. These results show similarities between the baclofen-mediated inhibition of cyclic AMP formation and glutamate release, suggesting a relationship between these two events. The baclofen-mediated inhibition of calcium influx may not be related to baclofen's inhibition of glutamate release.
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PMID:gamma-Aminobutyric acid-B receptors inhibit glutamate release from cerebellar granule cells: consequences of inhibiting cyclic AMP formation and calcium influx. 167 50

Cultured endothelium derived from three fractions of human cerebral microvessels was used to characterize dopamine (DA) receptors linked to adenylate cyclase activity. DA or D1 agonist, (+/-)-SKF-82958 hydrobromide, stimulated endothelial cyclic AMP formation in a dose-dependent manner. The selective D1 antagonist, (+/-)SCH-23390, inhibited in a dose-dependent manner the production of cyclic AMP induced by DA. The affinity for the D1 receptor appeared to be greater in endothelium derived from large and small microvessels than from capillaries. Cholera toxin ADP-ribosylation of Gs proteins abolished the DA stimulatory effect on endothelial adenylate cyclase, whereas pertussis toxin ADP-ribosylation enhanced the DA-inducible formation, indicating the presence of both D1 and D2 receptors. Agonists of alpha 1-adrenergic receptors (phenylephrine, 6-fluoronorepinephrine) or serotonin (5-HT), which stimulated the production of cyclic AMP, had no additive effect on DA-stimulated cyclic AMP formation. Incubation of these agents with DA produced the same or lower levels of cyclic AMP as compared to that formed by DA alone. The effect of alpha 1-adrenergic agonists or 5-HT on DA production of cyclic AMP was partially prevented by the D2 antagonist, S(-)-sulpiride, or ketanserin (5-HT2 greater than alpha 1 greater than H1 antagonists), respectively. These findings represent the first demonstration of D1- (stimulatory) and D2- (inhibitory) receptors linked to adenylate cyclase in microvascular endothelium derived from human brain. The data also indicate that dopaminergic receptors can interact with either alpha 1-adrenergic or or 5-HT receptors in endothelium on the adenylate cyclase level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopaminergic receptors linked to adenylate cyclase in human cerebromicrovascular endothelium. 168 Oct 36

D1 dopamine receptors on NS20Y neuroblastoma cells stimulate adenylate cyclase activity, whereas muscarinic receptors on the same cells negatively regulate adenylate cyclase. To determine the mechanisms which underlie these processes, cyclic AMP accumulation was measured in intact cells following either cholera or pertussis toxin treatment. Pretreatment with pertussis toxin (100 ng/ml), which ribosylated greater than 95% of inhibitory quinine nucleotide binding protein (Gi), caused the complete loss of muscarinic induced inhibition. Conversely, pertussis toxin did not affect the ability of dihydrexidine (1 microM, a full efficacy D1 agonist), PGE1 (100 nM), or forskolin (1 microM, a direct activator) to stimulate cAMP accumulation. Both the dihydrexidine-induced stimulation and the carbachol-induced inhibition of cyclic AMP accumulation were unaffected by either removal of extracellular calcium, or increased intracellular calcium caused by the addition of the calcium ionophore A23187. Cholera toxin dose- and time-dependently induced large accumulations of cAMP. At low cholera toxin concentrations, the effects of dihydrexidine (300 nM) were additive with those of cholera toxin. At cholera toxin concentrations greater than 100 ng/ml, dihydrexidine became ineffective in stimulating further cAMP synthesis. Conversely, forskolin (1 microM) still caused marked increases in cAMP accumulation after all cholera toxin treatments. Dihydrexidine-stimulated cAMP accumulation was additive with forskolin-stimulated cAMP accumulation at low forskolin concentrations (10 nM-3 microM), but synergistic at high concentrations (3-100 microM). Additionally, forskolin was much more potent after cholera toxin treatment, suggesting that an activated stimulatory guanine nucleotide binding protein (Gs) may be required for full activation of adenylate cyclase by forskolin in this cell type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Guanine nucleotide binding proteins and the regulation of cyclic AMP synthesis in NS20Y neuroblastoma cells: role of D1 dopamine and muscarinic receptors. 168 5

The present study examines the effect of chronic dopamine treatment, known to inhibit prolactin release from anterior pituitary, on two Ca2+ and K+ currents in cultured rat lactotrophs. K+ and Ca2+ currents were recorded using the whole-cell mode of the patch-clamp technique. The two types of voltage-dependent Ca2+ currents are called SD and FD (slowly deactivating and fast deactivating current component, respectively) and the two types of voltage-dependent K+ currents, IA and IK. All current types were isolated by tail current analysis. The amplitude of both normalized calcium components depended on the length of the culture (n = 48) while normalized amplitudes of both potassium currents remained constant (n = 9). Incubation of cells during 72 h with 50 microM of Actinomycin D, an inhibitor of mRNA synthesis, suggested that this increase in Ca2+ currents involved the synthesis of proteins. Long-lasting D2 receptor stimulation (8 days; 10 nM RU 24213) prevented this selective effect through activation of a pertussis toxin-sensitive G protein. We also examined whether cyclic adenosine-3',5'-cyclic-monophosphate (cyclic AMP) or Ca2+/phospholipid-dependent protein kinase (protein kinase C) could affect this development of channel activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic stimulation of D2 dopamine receptors specifically inhibits calcium but not potassium currents in rat lactotrophs. 168 31


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