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)

Endothelin-1 is a powerful inotropic peptide for the rat atrium. Its action can develop in the absence of L-type Ca2+ channel activity provided that the external Ca2(+)-concentration has been raised to supraphysiological concentrations. Endothelin stimulates phosphatidylinositol hydrolysis in new born rat atrial cells via a mechanism that is insensitive to pertussis toxin. The diacylglycerol/protein kinase C signaling pathway cannot account for the contractile action of endothelin but its activation by phorbol esters induces a partial desensitization of phospholipase C activity. Endothelin-1 and the related peptides, endothelin-2, endothelin-3, and sarafotoxin S6b, raise intracellular Ca2+ levels in rat atrial cells. The actions of endothelin-1, endothelin-2, and sarafotoxin on [Ca2+]i are mutually exclusive, suggesting that they act at the same receptor site. The rise in [Ca2+]i induced by endothelins results both from the mobilization of intracellular stores and from Ca2+ entry through the sarcolemma via a pathway that is not voltage-dependent L-type Ca2+ channels. The Ca2+ store that is mobilized in response to endothelin retains its Ca2+ content when cells were incubated for long periods of time in a 50 nM Ca2+ solution. It is insensitive to caffeine and ryanodine. These two properties distinguish it from the sarcoplasmic reticulum. Contraction experiments in which the pacing rate has been altered to favor Ca2+ accumulation into terminal cisternae of the sarcoplasmic reticulum also suggest that the Ca2+ load of the sarcoplasmic reticulum is increased in endothelin treated rat atria.
 ...
PMID:Endothelin mobilizes Ca2+ from a caffeine- and ryanodine-insensitive intracellular pool in rat atrial cells. 215 11

The methylxanthines, such as caffeine and theophylline, are an important and widely used class of drugs, which are believed to mediate many of their physiological effects by increasing intracellular concentrations of cAMP. These agents are known to inhibit phosphodiesterases and to block inhibitory A1 adenosine receptors in a competitive manner. Thus, the methylxanthines may increase cAMP accumulation by slowing its inactivation or by enhancing its production. Using a rat adipocyte membrane model we demonstrate that isobutylmethylxanthine (IBMX) induces a dose-dependent 34% increase in cAMP production above that produced by complete phosphodiesterase inhibition with papaverine. This stimulatory effect is dependent upon the inhibitory guanine nucleotide regulatory protein G1, in that inactivation of Gi by pertussis intoxication ablates IBMX-mediated stimulation of adenylate cyclase activity. Because the Gi-dependent effect of IBMX results in increased cAMP production, the mode of action is likely blockade of Gi activity. Accordingly, the capacity of GTP itself to inhibit adenylate cyclase activity is attenuated by IBMX. In contrast to Gi blockade induced by pertussis toxin, this heretofore unappreciated stimulatory mechanism is completely reversed by inhibitory receptor agonists. This mechanism of action may be responsible for certain physiological effects of methylxanthines, which are not easily explained by phosphodiesterase inhibition or antagonism of A1 adenosine receptors.
 ...
PMID:Isobutylmethylxanthine stimulates adenylate cyclase by blocking the inhibitory regulatory protein, Gi. 245 59

1. Voltage-sensitive calcium channel currents carried by Ca2+ (ICa) or Ba2+ (IBa) were followed by tail currents carried by Cl- ions in approximately 45% of cultured dorsal root ganglion neurones. 2. Extracellular application of (-)-baclofen (100 microM) inhibited IBa and ICl(Ba). Bay K 8644 (5 microM) potentiated both currents. 3. Intracellular GTP-gamma-S increased the proportion of neurones in which ICl(Ba) was recorded. In addition, the activation by GTP-gamma-S of a pertussis toxin-sensitive GTP binding (G)-protein resulted in a steady increase in the Cl- tail current with time, despite a concurrent reduction in IBa. 4. Extracellular application of 10mM caffeine selectively reduced ICl(Ba) without significant change in IBa. When Ca2+ was the charge carrier, caffeine had little effect on ICl(Ca), and increased the inactivation of ICa. 5. We conclude that, in addition to being regulated by divalent cation entry through Ca2+ channels, the Cl- current is also regulated by G-protein activation. The mechanism of activation of ICl(Ba) may involve Ca2+ release from intracellular stores.
 ...
PMID:Modulation of divalent cation-activated chloride ion currents. 246 Jan 76

Exogenous GTP was required for the induction of Ca2+ release from smooth muscle SR by IP3 if endogenous GTP was depleted. NaN3 could function as a partial substitute for GTP as a cofactor for the IP3-induced Ca2+ release from the SR. In contrast to the IP3-induced Ca2+ release, caffeine-induced Ca2+ release from the SR did not require GTP. Pertussis toxin inhibited the IP3-induced Ca2+ release from the SR, whereas it had no effect on caffeine-induced Ca2+ release. These results indicate that in smooth muscle two different Ca2+ release-channels exist in the SR: (a) activated by IP3, and (b) activated by caffeine or Ca2+.
 ...
PMID:The specific GTP requirement for inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned vascular smooth muscle. 246 78

Dictyostelium discoideum amebae chemotax toward folate during vegetative growth and toward extracellular cAMP during the aggregation phase that follows starvation. Stimulation of starving amebae with extracellular cAMP leads to both actin polymerization and pseudopod extension (Hall et al., 1988, J. Cell. Biochem. 37, 285-299). We have identified an actin nucleation activity (NA) from starving amebae that is regulated by cAMP receptors and controls actin polymerization (Hall et al., 1989, J. Cell Biol., in press). We show here that NA from vegetative cells is also regulated by chemotactic receptors for folate. Our studies indicate that NA is an essential effector in control of the actin cytoskeleton by chemotactic receptors. Guided by a recently proposed model for signal transduction from the cAMP receptor (Snaar-Jagalska et al., 1988, Dev. Genet. 9, 215-225), we investigated which of three signaling pathways activates the NA effector. Treatment of whole cells with a commercial pertussis toxin preparation (PT) inhibited cAMP-stimulated NA. However, endotoxin contamination of the PT appears to account for this effect. The synag7 mutation and caffeine treatment do not inhibit activation of NA by cAMP. Thus, neither activation of adenylate cyclase nor a G protein sensitive to PT treatment of whole cells is necessary for the NA response. Actin nucleation activity stimulated with folate is normal in vegetative fgdA cells. However, cAMP suppresses rather than activates NA in starving fgdA cells. This indicates that the components of the actin nucleation effector are present and that a pathway regulating the inhibitor(s) of nucleation remains functional in starving fgdA cells. The locus of the fgdA defect, a G protein implicated in phospholipase C activation, is directly or indirectly responsible for transduction of the stimulatory chemotactic signal from cAMP receptors to the nucleation effector in Dictyostelium.
 ...
PMID:Transduction of the chemotactic signal to the actin cytoskeleton of Dictyostelium discoideum. 251 Oct 51

Skinned fibre experiments were conducted to determine if guanine nucleotide-binding proteins play a role in excitation-contraction coupling of skeletal muscle. By itself, the GTP-gamma S, a non hydrolysable GTP analogue was unable to induce calcium release from the sarcoplasmic reticulum, even at concentrations as high as 500 microM. However, calcium- or caffeine-induced calcium releases were enhanced by GTP-gamma S in micromolar concentrations. This response was blocked by GDP-beta S or Pertussis toxin. 32P-ADP-ribosylation catalysed by Pertussis toxin, radiolabelled G-protein alpha subunits in the range of 40 kDa on membrane subcellular fractions of rat skeletal muscle. Using Western blot analysis with antibodies raised against the bovine transducin, G-proteins were identified in frog and rat skeletal muscle subcellular fractions. In most of the muscle fractions (plasma membrane, T-tubules, triads, sarcoplasmic reticulum), the anti-beta subunit antibodies recognized a 36 kDa protein which comigrated with transducin beta subunit. It appears therefore that some of the G-proteins identified by ADP-ribosylation or immunostaining in several subcellular fractions from skeletal muscle, are implicated in the modulation of calcium release from sarcoplasmic reticulum. These results suggest that a Pertussis toxin sensitive G-protein is present at the loci of E-C coupling, and that it serves to regulate the calcium release.
 ...
PMID:G-protein dependent potentiation of calcium release from sarcoplasmic reticulum of skeletal muscle. 251 87

1. The effect of drugs on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of desmethylimipramine (DMI)-treated bullfrog paravertebral sympathetic ganglia was studied by radioimmunoassay. The adrenaline-induced hyperpolarization (Adh) in the tissue was recorded by means of the sucrose-gap technique. 2. In the presence of propranolol (1 microM) and DMI (0.5 microM), adrenaline (1 microM) significantly reduced the concentration of cyclic AMP in forskolin-treated ganglia. This effect was prevented by pertussis toxin (5 micrograms ml-1). 3. The relative potency for drugs which increased ganglionic cyclic AMP content was: 50 microM forskolin much greater than 5 mM fluoride greater than 2 mM fluoride greater than 2 mM isobutylmethylxanthine (IBMX) greater than 5 mM caffeine. In contrast, their relative potency for inhibition of the Adh was: 2 mM IBMX greater than 5 mM fluoride greater than 5 mM caffeine much greater than 2 mM fluoride greater than 50 microM forskolin. The Adh was unaffected by pertussis toxin (5 micrograms ml-1). 4. Although the Adh was slightly reduced by the extracellular application of 8-bromo (8-Br) cyclic AMP, the majority of the data suggest that the transduction mechanism underlying the Adh is independent of the intracellular cyclic AMP concentration and provide an example of an alpha 2-adrenoceptor-mediated response that occurs independently of inhibition of adenylate cyclase.
 ...
PMID:Elevation of intracellular cyclic AMP concentration fails to inhibit adrenaline-induced hyperpolarization in amphibian sympathetic neurons. 254 97

Effects of pertussis toxin on Ca2+ transients in rat arterial smooth muscle cells in primary culture were monitored, using quin 2-microfluorometry. In the presence or the absence of extracellular Ca2+, norepinephrine, histamine, caffeine and high extracellular K+ induced elevations in cytosolic Ca2+ concentration. Cytosolic Ca2+ elevations induced by norepinephrine and histamine were inhibited by pretreatment of the cells with pertussis toxin, time- and dose-dependently. However, elevations induced by caffeine and K+-depolarization were unaffected by the pretreatment with this toxin. Thus, it is suggested that GTP binding protein, a pertussis toxin substrate and involved in the receptor-mediated cytosolic Ca2+ transients, is not involved in transient elevations in cytosolic Ca2+ induced by caffeine and K+-depolarization in cultured vascular smooth muscle cells.
 ...
PMID:Inhibition of calcium transients in cultured vascular smooth muscle cells by pertussis toxin. 309 16

The nonapeptide bradykinin (BK) activates sensory neurons and stimulates the transmission of nociceptive information into the CNS. We investigated the effect of this peptide on rat dorsal root ganglion neurons (DRG) grown in vitro. BK stimulated the synthesis of inositol trisphosphate (IP3) and the breakdown of phosphatidylinositol bisphosphate, the synthesis of diacylglycerol, and the release of arachidonic acid from DRG cells. The release of IP3 and arachidonic acid was not inhibited by pretreatment of the cells with pertussis toxin. BK also mobilized intracellular Ca2+ stores in DRG cells as assessed by fura-2-based microfluorimetry. Two types of Ca2+ stores appeared to exist in DRG neurons. One type could be mobilized by caffeine (10(-2) M), and this effect could be blocked by ryanodine in a use-dependent manner. These stores occurred primarily in the cell soma and were virtually absent from cell processes. A second type of store could be mobilized by BK, presumably through the mediation of IP3. These latter stores were distributed equally between the cell soma and processes. Experiments with combinations of caffeine and BK suggested that the stores mobilized by these 2 agents may be separate entities. Both the caffeine and BK sensitive Ca2+ storage sites appeared to participate in buffering a Ca2+ load induced in DRG neurons by cell depolarization. The relevance of these observations to the mechanism of action of BK on sensory neurons is discussed.
 ...
PMID:Regulation of calcium homeostasis in sensory neurons by bradykinin. 318 14

The effects of chronic caffeine on the A1 adenosine receptor-adenylate cyclase system of rat cerebral cortical membranes were studied. Caffeine treatment significantly increased the number of A1 adenosine receptors as determined with the A1 adenosine receptor antagonist radioligand [3H]xanthine amine congener (XAC). R-PIA (agonist) competition curves constructed with [3H]XAC were most appropriately described by a two affinity state model in control membranes with a KH of 2.1 +/- 0.8 and a KL of 404 +/- 330 nM with 50 +/- 4% of receptors in the high affinity state (%RH). In contrast, in membranes from treated animals, there was a marked shift towards the high affinity state. In three of seven animals all of the receptors were shifted to a unique high affinity state which was indistinguishable from the KH observed in membranes from control animals. In four of seven animals the %RH increased from 50 to 69% with KH and KL indistinguishable from the control values. Thus, the agonist specific high affinity form of the receptor was enhanced following caffeine treatment. Maximal inhibition of adenylate cyclase activity in cerebral cortical membranes by R-PIA (1 microM) was significantly increased by 28% following caffeine treatment, consistent with an increased coupling of receptor-Gi protein with adenylate cyclase. Importantly, the quantity of Gi (alpha i) in rat cerebral cortex, determined by pertussis toxin-mediated labeling, was also increased to 133% of control values by this treatment. Thus, multiple components and interactions of the A1 adenosine receptor-adenylate cyclase complex are regulated by caffeine. These changes are likely compensatory measures to offset blockade of A1 receptors in vivo by caffeine and lead to a sensitization of this inhibitory receptor system.
 ...
PMID:Multiple components of the A1 adenosine receptor-adenylate cyclase system are regulated in rat cerebral cortex by chronic caffeine ingestion. 339 8


<< Previous 1 2 3 4 5 6 7 8 9 Next >>