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 intact NIH 3T3 murine fibroblasts, prostaglandins (PGs) F2 alpha and E2 induce dose-dependent stimulation of inositol monophosphate generation. PGF2 alpha is greater than 50-fold more potent than PGE2 in eliciting this response. In streptolysin O-permeabilized NIH 3T3 cells, PGF2 alpha and PGE2 induced dose-dependent accumulations of inositol bis- and trisphosphates, which were dependent on the presence of the guanine nucleotide guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) (10 microM). Pretreatment of cells for 16 hr with 100 nM PGF2 alpha resulted in a significant reduction of not only subsequent PGF2 alpha- and PGE2-induced but also GTP gamma S-induced stimulation of inositol phosphate formation in permeabilized cells. PGF2 alpha-induced accumulation of inositol phosphates was partially inhibited by pretreatment with pertussis toxin (1 microgram/ml, 4 hr). The inhibition by pertussis toxin was small but was not related to cyclic AMP formation, because forskolin, which activates adenylate cyclase, did not mimic pertussis toxin-induced inhibition. In the same cell line, PGF2 alpha and PGE2 induced a dose-dependent accumulation of cAMP and a dose-dependent potentiation of 0.5 microM forskolin-stimulated cAMP formation. PGF2 alpha and PGE2 were almost equipotent in eliciting both responses. However, PGF2 alpha was less efficacious than PGE2 and, in the presence of forskolin, PGF2 alpha at 10 microM induced an inhibitory effect on cAMP accumulation. Such inhibition may be related to PGF2 alpha-mediated phospholipase C activation and subsequent stimulation of protein kinase C, because the phorbol ester phorbol 12-myristate-13-acetate, which directly activates protein kinase C, also inhibited forskolin- and PGE2-induced cAMP accumulation. Pretreatment with PGF2 alpha for 16 hr did not reduce subsequent stimulation of cAMP accumulation by PGF2 alpha or PGE2. The results indicate that in NIH 3T3 cells two receptors for PGs are present, one that couples to adenylate cyclase, probably through Gs, and does not exhibit selectivity between PGF2 alpha and PGE2 and a second receptor that couples to phospholipase C through a guanine nucleotide-binding protein that is not sensitive to pertussis toxin pretreatment. The latter shows at least 40-fold selectivity towards PGF2 alpha over PGE2. Because long treatment with PGF2 alpha resulted in desensitization of the GTP gamma S-induced response, it is possible that long exposure to PGF2 alpha may down-regulate the guanine nucleotide-binding involved in phospholipase C signal transduction.
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PMID:Prostaglandin receptors in NIH 3T3 cells: coupling of one receptor to adenylate cyclase and of a second receptor to phospholipase C. 165 2

The developmental changes in the beta-adrenergic receptor/cyclic AMP generating system were examined using mouse cerebral cortical neurons in primary culture. During neuronal growth in vitro, the number of binding sites for [3H]dihydroalprenolol (DHA) showed a tendency to increase (Bmax), while the affinity (Kd) for [3H]DHA did not show any noticeable changes. Basal and isoproterenol-stimulated adenylate cyclase activities as well as the activation of adenylate cyclase by 5'-guanylylimidodiphosphate (GppNHp), NaF and forskolin showed progressive and parallel increases during neuronal growth on a polylysine-coated surface. The treatment of primary cultured neurons with islet-activating protein (IAP), one of the pertussis toxins, attenuated the inhibitory effect of carbachol, a muscarinic agonist, on isoproterenol-induced activation of adenylate cyclase activity. These results indicate that primary cultured neurons possess a cyclic AMP generating system coupled with beta-adrenergic and muscarinic receptors, which is regulated via stimulatory and inhibitory GTP-binding proteins, respectively. The results described above also suggest that the beta-adrenergic receptor, stimulatory and inhibitory types of GTP-binding proteins and adenylate cyclase may develop in a parallel fashion during neuronal growth on a polylysine-coated surface.
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PMID:Ontogeny of beta-adrenergic receptor-mediated cyclic AMP generating system in primary cultured neurons. 165 19

1. Agonist activation of rat retina muscarinic receptors results in suppression of cyclic AMP (cAMP) generation and enhanced phosphoinositide hydrolysis. 2. Pharmacological manipulations that elevate cAMP or stable analogues of cAMP attenuate the acetylcholine (ACh)-induced enhancement of phosphoinositide hydrolysis. We postulate that cross-talk between adenylate cyclase and phospholipase C signal transducing systems probably exists in rat retina, as has been described for other systems. 3. Intraocular administration of pertussis toxin attenuated the response of both adenylate cyclase and phospholipase C to muscarinic stimulation, suggesting that some retinal muscarinic receptors are apparently coupled to their effector systems via pertussis toxin sensitive G proteins.
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PMID:Modulation of muscarinic receptor-mediated adenylate cyclase and phospholipase C responses in rat retina. 166 Mar 49

Calcitonin (CT) is a well-known inhibitor of osteoclastic bone resorption both in vivo and in vitro. The effect is mediated by activation of adenylate cyclase and subsequent increased levels of cyclic AMP (cAMP). We report here that CT-induced (30 nmol/liter) accumulation of cAMP in cultured neonatal mouse calvaria is enhanced two-fold by 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nmol/liter) and phorbol 12,13-dibutyrate (PDBU; 100 nmol/liter), two protein kinase C (PKC)-activating phorbol esters, whereas phorbol 13-monoacetate (phorb-13; 100 nmol/liter), a related compound that does not activate PKC, has no effect. The ability of TPA and PDBU to enhance CT-stimulated cAMP accumulation was obtained also in the presence of indomethacin (1 mumol/liter). Kinetic studies revealed that TPA enhanced the cAMP response to CT at all the time points at which CT had a significant effect per se and that TPA did not alter the time-course of the cAMP response to CT. Treatment with pertussis toxin (100 ng/ml) enhanced cAMP response to parathyroid hormone (10 nmol/liter) and prostaglandin E2, but not to CT. From these data it is concluded that PKC, but not pertussis toxin-sensitive guanyl nucleotide-binding proteins (G-proteins), can interact with and modify the signal transducing system for CT in osteoclasts.
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PMID:Effects of phorbol esters and pertussis toxin on calcitonin-stimulated accumulation of cyclic AMP in neonatal mouse calvarial bones. 166 13

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


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