Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free cells isolated from adult rat heart by the collagenase method were maintained in culture up to 21 h with or without an islet-activating protein (IAP) that had been purified from the culture medium of Bordetella pertussis. Short-term stimulation of beta-adrenergic or glucagon receptors in these cultured cells caused more accumulation of cAMP in cells precultured with IAP (IAP-treated) than in nontreated cells, although there was no significant difference in the baseline (non-stimulated) content of cAMP between these cells. Stimulation of muscarinic cholinergic or adenosine R-site receptors caused a marked inhibition of cAMP accumulation in nontreated cells in either the presence or absence of a beta-agonist (or glucagon); no such inhibition was essentially observed in IAP-treated cells. These actions of IAP developed gradually and were dose-dependent with the half-maximal concentration of approximately 80 ng/ml in culture. It is concluded that IAP may exert its unique influence on the heart cell membrane causing profound modification of the coupling mechanism involved in the receptor-mediated activation or inhibition of adenylate cyclase. This action of IAP differs clearly from that of cholera toxin which activates adenylate cyclase rather independently of the receptor functions in heart cells.
 ...
PMID:Modification by islet-activating protein of receptor-mediated regulation of cyclic AMP accumulation in isolated rat heart cells. 616 42

Membranes were obtained from Xenopus laevis oocytes after removal of follicular cells by collagenase treatment. [32P]ADP-ribosylation with pertussis toxin showed them to contain a single Mr = 40000 substrate for this toxin that co-migrates on sodium dodecylsufate-polyacrylamide gel electrophoresis with pure human erythrocyte Ni, the inhibitory regulatory component of adenylyl cyclase. [32P]ADP-ribosylation of oocyte membranes with cholera toxin also showed presence of a single substrate but of Mr = 42000. These results indicate, that the adenylyl cyclase system of oocytes, like that of somatic cells and unlike that of spermatozoids, contains the catalytic unit C and both of the known regulatory N components. The possible susceptibility to pertussis toxin of the guanine nucleotide-dependent inhibition of oocyte adenylyl cyclase by progesterone was investigated. This action of progesterone is mediated by a membrane bound receptor as opposed to a receptor of cytosolic or nuclear localization. However, the inhibitory effect of progesterone was unaffected by pertussis toxin, even though the oocyte membrane Ni was fully ADP-ribosylated with pertussis toxin, as revealed by lack of further [32P]ADP-ribosylation on subsequent re-incubation with pertussis toxin. These results indicate that the action of progesterone, in spite of being nucleotide-dependent, is either not mediated by Ni, suggesting the existence of an additional nucleotide regulatory component, or if mediated by Ni, involves a mode of regulation of this coupling protein that is different from that by which all other inhibitory hormones act on adenylyl cyclase.
 ...
PMID:Oocyte adenylyl cyclase contains Ni, yet the guanine nucleotide-dependent inhibition by progesterone is not sensitive to pertussis toxin. 643 46

We have evaluated the inhibitory effect of dopamine on PRL secretion induced by blocking K+ channels. Tumor-derived GH4C1 cells and collagenase-dispersed normal anterior pituitary (AP) cells from young adult male rats were perifused with Krebs-Ringer Hepes medium. In both cell types blocking K+ channels with tetraethylammonium (TEA) induced PRL secretion but did not stimulate cyclic AMP generation. Blocking Na+ channels with 1 microM tetrodotoxin had no effect on basal or TEA-induced PRL secretion. Dopamine inhibited the TEA-induced rise in [Ca2+]i in GH4C1 cells expressing dopamine D2 short receptors. In normal AP cells, 1-100 nM dopamine blocked PRL secretion induced by 20 mM TEA in a log-linear concentration-dependent fashion, with a plateau at > 100 nM dopamine (IC50 30 nM). The D2 dopaminergic receptor agonist, quinpirole, at 100 nM completely blocked PRL secretion induced by 20 mM TEA. The D2 dopaminergic receptor antagonist, sulpiride, at 10 microM reversed the inhibitory effect of 10 microM dopamine on PRL secretion induced by 20 mM TEA. Pretreatment of cells with 100 ng/ml pertussis toxin (PTX) for 24 h prevented 100 nM dopamine inhibition of PRL secretion induced by 20 mM TEA. The data indicate that in both normal lactotroph cells and in tumor-derived cells expressing D2 receptors, PRL secretion stimulated by blocking K+ channels is inhibited by dopamine binding to D2 receptors on the plasma membrane. This inhibition involves interaction with PTX-sensitive Gi protein.
 ...
PMID:Pituitary PRL secretion induced by tetraethylammonium is inhibited by dopamine through D2 receptors. 748 18

The present study was undertaken to determine if acute stress induced by exposure to ether resulted in the presence of beta-cell-tropic factors in rat plasma and if this insulinotropic activity was increased by pertussis toxin. Rats pretreated with pertussis toxin (5 micrograms/kg, 5 days previously) showed marked hyperinsulinemia, but only after exposure to ether before blood sampling. This hyperinsulinemia was not modified by adrenal demedullation. Effects on insulin secretion were assessed by incubation of plasma (diluted with Krebs buffer) with collagenase-isolated rat pancreatic islets. When blood was collected by decapitation from normal rats, the subsequently prepared plasma (12.5% to 50%) profoundly inhibited insulin release from rat isolated islets. This inhibition was probably mediated by catecholamines, since it was not seen with plasma from adrenal-demedullated rats and was prevented by alpha 2-adrenoceptor-blocking drugs. Plasma from adrenal-demedullated, pertussis toxin-treated rats stimulated insulin secretion (by 60%) when the donor rats had been exposed to ether before blood sampling. It is suggested that stress may result in the presence of circulating beta-cell-tropic factors, which may contribute to the acute stress-induced hyperinsulinemia seen in pertussis toxin-treated animals.
 ...
PMID:Acute stress-induced hyperinsulinemia in the pertussis toxin-treated rat: possible role of humoral beta-cell-tropic factors. 793 72

Cortisol inhibits growth hormone (GH) release in short-term culture and is stimulatory in long-term cultures of rat and human pituitary cells. This study sought to determine the in vitro effects of cortisol on GH release and the signal transduction pathways mediating the effects of cortisol on GH release from cultured ovine somatotrophs. Pituitary cells were dispersed with collagenase and placed in culture medium for 4 days. The data indicate that cortisol inhibited growth hormone-releasing hormone (GHRH)-stimulated GH release by at least 2 h. In short-term culture GHRH-, forskolin- and dibutyryl cyclic AMP-stimulated GH release were inhibited by cortisol, suggesting an effect distal to the membrane and involving a protein kinase A (PKA)-dependent pathway. GH release initiated by KCl was inhibited by cortisol, but GH release caused by the calcium ionophore A23187 was unaffected. This suggests a possible action of cortisol on the calcium channels. The inhibition by cortisol of the calcium-dependent secretion of GH release appeared to play a smaller role in mediating cortisol inhibition of GH release than that seen with PKA. Attempts to overcome cortisol inhibition of GH release using puromycin, arachidonic acid or pertussis toxin were unsuccessful. Since cortisol inhibition of GH release does not occur via the mechanisms found in other cell types, cortisol inhibition of pituitary cell secretions appears to be cell-specific rather than utilizing a single inhibitory mechanism. The majority of cortisol actions on the somatotroph appear to act at a site distal to the production of cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cortisol inhibition of growth hormone-releasing hormone-stimulated growth hormone release from cultured sheep pituitary cells. 807 50

Hepatocytes isolated from rats by the collagenase perfusion method were cultured as monolayers at concentrations of 0.4-1.1 x 10(6) attached cells/dish (9 cm2) for 1-3 days and the effect of prostaglandins on their glycogenolysis was studied. By use of [14C]glycogen-labeled cells, prostaglandin E2 (PGE2) was found to have a stimulatory effect on glycogen degradation at high cell density (more than 0.8 x 10(6) cells/dish) in 1-day cultures. PGE2 was maximally effective at 10(-7) M, increasing [14C]release from cellular [14C]glycogen to 2-3 times the basal level after 1 h incubation, and to plateau level within 2 h. PGE1, 16,16-dimethyl PGE2 and PGF2 alpha had similar effects, but PGD2 and dinor-PGE1 (a metabolite of PGE1 and PGE2 in hepatocytes) had no effect. This prostaglandin-induced glycogen degradation was observed in 1-day cultures, with a maximum between 20-30 h, but not in 2-day and later cultures. Treatment of hepatocytes with pertussis toxin potentiated PGE2-stimulated glycogen degradation, indicating that the effect involves a different pathway from that for inhibition of glucagon- and epinephrine-stimulated glycogenolysis by E series prostaglandins reported previously.
 ...
PMID:Stimulation of glycogen degradation by prostaglandin E2 in primary cultured rat hepatocytes. 832 15

1. Prostaglandin E2 (PGE2) is an autacoid that decreases proteoglycan synthesis, increases metalloprotease production by cultured chondrocytes, and can modulate some of the actions of interleukin-1 on cartilage. The objective of the present study was to characterize the subtype of prostaglandin E2 receptor present in bovine chondrocytes in culture. 2. Primary cultures of articular chondrocytes were prepared from slices of bovine carpal cartilage by sequential digestion with type III hyaluronidase, trypsin, type II collagenase, followed by overnight incubation in Dulbecco's Modified Eagle's Medium (DMEM) with type II collagenase, washing, and seeding at a density of 2 x 10(5) cells cm-2 in DMEM with 10% foetal bovine serum. 3. PGE2 and carbaprostacyclin induced dose-dependent increases in intracellular cyclic AMP in bovine chondrocytes in culture. The potencies of these compounds were different, and maximal doses of PGE2 and carbaprostacyclin had an additive effect. PGD2 induced a small increase in intracellular cyclic AMP only at a high concentration (10(-5) M). 4. PGE2 was more potent that the EP2 agonist 11-deoxy-PGE1 at inducing increases in intracellular cyclic AMP. The EP2 agonist butaprost, however, induced only a small increase at a concentration of 10(-5)M. 17-Phenyl-PGE2 (EP1 agonist), sulprostone and MB 28767 (15S-hydroxy-9-oxo-16-phenoxy-omega-tetranorprost-13E-enoic acid) (EP3 agonists) did not induce an increase in intracellular cyclic AMP at concentrations up to 10(-5)M. 5. The EP4 antagonist AH 23848B ([1 alpha(Z),2 beta, 5 alpha]-(+/-) -7-[5-[[(1,1'-biphenyl)-4-yl]methoxyl-2-(4-morpholinyl) -3-oxocyclopentyl]-5-heptenoic acid) antagonized PGE2 but not carbaprostacyclin effects on intracellular cyclic AMP. The Schild plot slope was different from 1 but this could be due to an interaction of PGE2 with IP receptors in high doses. The exact nature of the antagonism by compound AH 23848B could not be definitely established in these experimental conditions. 6. Neither PGE2 nor any of its analogues inhibited the increase in intracellular cyclic AMP induced by forskolin, and pertussis toxin did not alter the response to PGE2, suggesting that no Gi-coupled PGE2 receptors are present in these cells. Stimulation with PGE2 did not induce significant increases in intracellular inositol-trisphosphate levels nor increases in intracellular free calcium as determined by confocal microscopy, suggesting the absence of phospholipase-C-coupled or of calcium channel-coupled PGE2 receptors in bovine chondrocytes in these experimental conditions. 7. These results show for the first time that bovine chondrocytes in culture present a functional PGE2 receptor that has some pharmacological characteristics of an EP4 subtype, as well as an IP receptor.
 ...
PMID:Characterization of the PGE2 receptor subtype in bovine chondrocytes in culture. 884 20

To determine whether G proteins are involved in the regulation of mouse placental lactogen-I (mPL-I) and/or mPL-II secretion before midpregnancy, mouse placental tissue from day 7 of pregnancy was dispersed with collagenase, cells were fractionated on a percoll gradient, and the purified trophoblast cells were cultured in a serum-free medium with cholera toxin (CTX) or pertussis toxin (PTX) which modulate the activities of distinct G proteins for 5 days. CTX inhibited both mPL-I and mPL-II secretion, but PTX inhibited mPL-I secretion and stimulated mPL-II secretion in a time- and dose-dependent manner. Addition of both CTX and PTX additionally inhibited mPL-I secretion but did not affect mPL-II secretion. 8-Bromo cAMP, which increases intracellular cAMP accumulation, inhibited both mPL-I and mPL-II secretion similarly to CTX. In contrast, H8, an inhibitor of cAMP-dependent protein kinase A, stimulated both mPL-I and mPL-II secretion. Addition of PTX and H8 synergistically stimulated mPL-II secretion. These findings suggest that G proteins play important roles in regulation of mPL-I and mPL-II secretion before midpregnancy.
 ...
PMID:Regulation of mouse placental lactogen secretion by G proteins before midpregnancy. 890 70

The expression and function of stimulatory adenosine A2 receptor on the cardiac myocyte is not well defined. The objective of the present study is to characterize the A2a receptor in adult rat cardiac ventricular myocytes. After selection of an optimal lot of collagenase for myocyte isolation and for consistent measurement of adenosine-mediated responses, the A1-receptor pathway was inactivated by pertussis toxin and by the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine. Effects of the adenosine agonist and antagonist or cardiac myocyte contractile amplitude and on adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined. The A2a-receptor-selective agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoade nos ine (CGS-21680) caused a pronounced stimulation of myocyte contractile amplitude and an increase in the cAMP level, as did the nonselective agonists 5'-(N-ethylcarboxamido) adenosine (NECA) and adenosine. The A2a-receptor-selective antagonist 8-(3-chlorostyryl)caffeine blocked the NECA- and adenosine-induced positive inotropic response. Probing of myocyte RNA with a rat A2a-receptor cDNA demonstrated a 2.6-kb mRNA, corresponding to that encoding the A2a receptor. Together, data from contractile, cAMP, and RNA studies indicate that A2a receptors are expressed and are functionally coupled to stimulation of cAMP accumulation and cardiac contractility in adult rat ventricular myocytes.
 ...
PMID:Characterization of a stimulatory adenosine A2a receptor in adult rat ventricular myocyte. 892 71

1. Growth hormone (GH) secretion from the anterior pituitary gland is mainly regulated by hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIF). Somatostatin reduces both spontaneous and GHRH-stimulated GH secretion. 2. Exocytosis of GH is mainly determined by the intracellular free Ca2+ concentration ([Ca2+]i), which is regulated by the influx of Ca2+ via membrane Ca2+ channels. Somatostatin reduces the influx of Ca2+ through two separate mechanisms, namely a direct action on Ca2+ channels and an indirect action on membrane potentials through the activation of K+ channels. 3. In the present experiments, somatotroph-enriched cells were obtained from the ovine pituitary gland by means of collagenase dissociation and Percoll-gradient centrifugation. Further identification was based on the effect of SRIF (10 nmol/L) on Ca2+ or K+ currents. 4. A significant reduction in Ca2+ currents and an increase in K+ currents was obtained in response to local application of SRIF (10 nmol/L), but vehicle application had no effect. The responses of Ca2+ and K+ currents to SRIF were reversible after removal of SRIF. 5. Dialysis of GTP-gamma-s (200 mumol/L) abolished the recovery phase of K+ current response to SRIF after its removal, whereas GDP-beta-s (200 mumol/L) totally blocked the response. Pretreatment of the cells with pertussis toxin (100 nmol/L) overnight abolished the Ca2+ current response to SRIF. 6. Intracellular dialysis of antibodies to alpha o, alpha i1-3, alpha i1-2 and alpha i3 subunits of the G-proteins into cells via whole-cell patch-clamp pipettes was confirmed by immunofluorescent staining of the antibodies. 7. Dialysis of anti-alpha i1-3 or anti-alpha i3 antibodies significantly attenuated the increase in the K+ current in response to 10 nmol/L SRIF, whereas neither anti-alpha o nor anti-alpha i1-2 antibodies diminished the effect of SRIF on the K+ current. 8. Dialysis of anti-alpha o antibodies significantly attenuated the reduction in the Ca2+ current that was obtained upon application of 10 nmol/L SRIF. Neither anti-alpha i1-2 nor anti-alpha i3 antibody dialysis diminished the effect of SRIF on the Ca2+ current. 9. Dialysis of the alpha o common antisense oligonucleotides (ASm) but not the alpha i3 AS significantly diminished the inhibitory effect of SRIF on the Ca2+ current. This effect of alpha o ASm dialysis occurred at 12 h incubation after dialysis, reaching a maximal level at 48 h and partially recovering at 72 h incubation. Antisense oligonucleotides specific for alpha o1 (alpha o1 AS) or alpha o2 (alpha o2 AS) were dialysed into somatotrophs and only alpha o2 AS significantly attenuated the inhibition of SRIF on the Ca2+ current. 10. It is concluded that the Gi3 protein mediates the effect of SRIF on the K+ current and that the G(o)2 protein mediates the effect of SRIF on the Ca2+ current in primary cultured ovine somatotrophs.
 ...
PMID:G(o)2 and Gi3 proteins mediate the action of somatostatin on membrane Ca2+ and K+ currents in ovine pituitary somatotrophs. 926 41


<< Previous 1 2 3 4 Next >>