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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calmodulin-activated adenylate cyclase of Bordetella pertussis and Bacillus anthracis are two cognate bacterial toxins. Three short regions of 13-24 amino acid residues in these proteins exhibit between 66 and 80% identity. Site-directed mutagenesis of four residues in B. pertussis adenylate cyclase situated in the second (Asp188, Asp190) and third (His298, Glu301) segments of identity were accompanied by important decrease, or total loss, of enzyme activity. The calmodulin-binding properties of mutated proteins showed no important differences when compared to the wild-type enzyme. Apart from the loss of enzymatic activity, the most important change accompanying replacement of Asp188 by other amino acids was a dramatic decrease in binding of 3'-anthraniloyl-2'-deoxyadenosine 5'-triphosphate, a fluorescent analogue of ATP. From these results we concluded that the two neighbouring aspartic acid residues in B. pertussis adenylate cyclase, conserved in many other ATP-utilizing enzymes, are essential for binding the Mg(2+)-nucleotide complex, and for subsequent catalysis. Replacement of His298 and Glu301 by other amino acid residues affected the nucleotide-binding properties of adenylate cyclase to a lesser degree suggesting that they might be important in the mechanism of enzyme activation by calmodulin, rather than being involved directly in catalysis.
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PMID:Functional consequences of single amino acid substitutions in calmodulin-activated adenylate cyclase of Bordetella pertussis. 205 Jan 7

3'-Anthraniloyl-2'-deoxyadenosine 5'-triphosphate (Ant-dATP), a fluorescent analogue of ATP, was tested as a probe for the nucleotide-binding site of calmodulin (CaM)-activated adenylate cyclases from Bordetella pertussis (BPCYA47) and Bacillus anthracis (BACYA62). Ant-dATP competitively inhibited both bacterial enzymes expressed in Escherichia coli (ki approximately 10 microM). Binding of the analogue to adenylate cyclase was monitored by equilibrium dialysis and by an increase in its fluorescence emission at 420 nm upon excitation at 330 nm. Whereas the fluorescence of Ant-dATP was little influenced by divalent cations, CaM, or adenylate cyclase alone, the Ca2+.CaM.cyclase complex increased up to 4 times the quantum yield of Ant-dATP. Binding of the analogue to the catalytic site of BPCYA47 and BACYA62 was specific as shown by its displacement with ATP or 3'-dATP. Our results substantiate the role of CaM in favoring substrate binding to CaM-activated enzymes.
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PMID:Binding of 3'-anthraniloyl-2'-deoxy-ATP to calmodulin-activated adenylate cyclase from Bordetella pertussis and Bacillus anthracis. 217 37

2',5'-Dideoxyadenoside (DDA) inhibited both anti-IgE and ionophore A23187 induced histamine secretion from human basophils. Whereas DDA inhibited IgE-dependent histamine secretion when added at all times prior to challenge, release induced by A23187 was inhibited only with simultaneous addition of DDA and secretagogue. Dipyridamole, but not theophylline, abrogated DDA mediated inhibition of histamine release suggesting an intracellular mechanism of action of DDA. The observations that 2'-deoxyadenosine and 9-beta-D-arabinofuranosyladenine also inhibited release suggest that the its inhibitory effect was enhanced by manganese and reversed by islet activating protein from Bordetella pertussis suggest that DDA inhibits basophil histamine release by interacting with a guanine nucleotide binding protein which may be linked to either adenylate cyclase or other second messenger system(s).
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PMID:Inhibition of immunological and nonimmunological histamine release from human basophils by adenosine analogues that act at P-sites. 242 53

1. Neurons with a receptor responded to FMRFamide (Phe-Met-Arg-Phe-NH2) were identified in the ganglion of Aplysia kurodai. Ionic mechanism and channel gating system of the FMRFamide-induced responses were investigated by current clamp and voltage clamp methods. 2. The reversal potential of FMRFamide-induced response exactly coincided with the equilibrium potential for K+. This proved that the response was produced by a specific increase in membrane permeability toward K+, exclusively. 3. The FMRFamide-induced response was not affected by the inhibitors for Ca2(+)-activated K(+)-current, i.e., TEA, apamin, and EGTA. This excluded a possibility that FMRFamide-activated K(+)-channel is a Ca2(+)-activated K(+)-channel. 4. Intracellular injection of pertussis-toxin (PTX) caused no change in either resting potential or conductance, but it irreversibly blocked the FMRFamide-induced outward current within 30 min. Similarly applied cholera toxin (CTX) showed no effect on the FMRF-amide response. 5. Intracellular application of guanosine 5'-0-(2-thiodiphosphate) (GDP beta S) caused no effect on either resting potential or conductance, but it blocked the FMRFamide-induced K(+)-current within 3 min. 6. Intracellular application of guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) alone induced a slowly developing, irreversible outward current associated with an increase in membrane conductance. However, repetitive applications of FMRFamide immediately after the start of GTP gamma S application markedly facilitated the effect of GTP gamma S on the resting membrane. 7. Intracellular application of either adenylate cyclase inhibitor (3'-deoxyadenosine) or A-kinase inhibitor (H-8) did not affect the FMRFamide-induced response. 8. It was concluded that the FMRFamide-induced K(+)-current is mediated by PTX-sensitive GTP-binding protein Gi, Go or Gk. It was also suggested that the FMRFamide-induced response is produced independently of the changes in intracellular Ca2+ or cyclic AMP.
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PMID:[The gating mechanism of K(+)-channels coupled to the FMRFamide receptor in the ganglion cells of Aplysia]. 255 80

Gentamicin nucleotidyltransferase-catalyzed reaction of (Sp)-[alpha-17O]dATP with tobramycin produced 2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin. The configuration at phosphorus in this product was shown to be Rp by chemical degradation to chiral [17O, 18O]dAMP using a stereochemically defined procedure, and determination of the configuration at phosphorus in this product. Periodate-base treatment of 2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin followed by NaBH4 reduction produced (2-glyceryl)-[17O]dAMP, which upon snake venom phosphodiesterase-catalyzed hydrolysis in H(2)18O produced [17O,18O] dAMP. The configuration at phosphorus in this product was shown to be S by enzymatic phosphorylation to [17O,18O]dATP, adenylylcyclase (Bordetella pertussis)-catalyzed cyclization to 3',5'-cyclic [17O,18O]dAMP, and 31P NMR analysis of the ethyl esters. Since snake venom phosphodiesterase-catalyzed hydrolyses proceed with retention of configuration at phosphorus, (Sp)-[17O,18O]dAMP must have been produced from (Rp)-(2-glyceryl)-[17O]dAMP; and since the chemical degradation to the latter compound did not involve cleavage of any bonds to phosphorus, the initial enzymatic product must have been (Rp)-2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin. Therefore, nucleotidyl transfer catalyzed by gentamicin nucleotidyl-transferase proceeds with inversion of configuration at phosphorus, and the reaction mechanism involves an uneven number of phosphotransfer steps. Inasmuch as this is an uncomplicated two-substrate group transfer reaction, the mechanism probably involves direct nucleotidyl transfer from the nucleoside triphosphate to the aminoglycoside. The B. pertussis adenylylcyclase reaction was shown to proceed with inversion at phosphorus, as has been established for other adenylylcyclases.
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PMID:Gentamicin nucleotidyltransferase. Stereochemical inversion at phosphorus in enzymatic 2'-deoxyadenylyl transfer to tobramycin. 287 83

1. To address the questions of whether beta-adrenoreceptor stimulation can augment ATP-sensitive potassium current (IK(ATP)), and what the mechanism of such an effect might be, action potentials and whole-cell ionic currents were recorded from adult cat cardiac ventricular myocytes using a conventional whole-cell patch technique. 2. An outwardly directed, ohmic, non-inactivating, glyburide (10 microM)-sensitive current reversing near the reversal potential for potassium (EK) developed slowly (10-25 min) in cells dialysed with an ATP-free pipette (intracellular) solution. During this time, action potential duration markedly decreased while the resting membrane potential hyperpolarized closer to EK. Extended (> 30 min) periods of internal dialysis with ATP-free solution eventually resulted in run-down of the outward current. 3. Externally applied isoprenaline (1 microM) caused a rapidly developing (< or = 60 s), sustained enhancement of a glyburide (10 microM)-sensitive IK(ATP) in cells internally dialysed with ATP-free solution. IK(ATP) remained elevated even after the isoprenaline was removed, and subsequent applications of the beta-agonist failed to increase IK(ATP) further. Half-maximal isoprenaline stimulation of IK(ATP) occurred at a concentration of approximate of 1.5 nM. 4. Pretreatment with propranolol (1 microM) prevented the enhancement of IK(ATP) by a beta-agonist. 5. Isoprenaline-induced IK(ATP) could be blocked by either internal application of GDP-beta-S (2-5 mM) or pretreatment with cholera toxin (1-10 microgram ml-1, > 18 h). Pretreatment with pertussis toxin (1-2 microgram ml-1, > 18 h) did not attenuate the isoprenaline response, whereas internally applied GTP-gamma-S (100 microM) or F- (20 mM) caused IK(ATP) to increase rapidly in the absence of the beta-agonist. 6. Although externally applied forskolin (10 microM) also stimulated IK(ATP), neither 1,9-dideoxyforskolin (10 microM) nor 8-(4-chlorophenylthio)-cAMP (200 microM) had any effect on the current. Internal application of the adenylate cyclase inhibitor 2'-deoxyadenosine-3'-monophosphate (100 microM) resulted in a reduction in the response to isoprenaline, while internal application of a protein kinase A inhibitor (PKI5-24, 22.5 microM) did not attenuate the response to the beta-agonist. 7. IK(ATP) developed slowly during internal dialysis with ATP-free solution.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Enhancement of ATP-sensitive potassium current in cat ventricular myocytes by beta-adrenoreceptor stimulation. 801 90

1. G protein betagamma subunits activate the acetylcholine-induced potassium current IK,ACh. There is no evidence of specificity at the level of the betagamma subunits. Therefore all G protein-coupled receptors in atrial myocytes should be able to activate IK,ACh. Paradoxically, it is often stated that isoprenaline does not activate IK,ACh. Rationales to explain this negative result include insufficient concentrations of Gs in the atrium or restricted access of Gs-derived betagamma subunits to the IK,ACh channel. We took advantage of a non-specific increase in Gs that results after infection with adenovirus. 2. Adenoviral infection unmasked a 1 microM isoprenaline-induced IK,ACh which was prevented by propranolol. Isoprenaline occasionally activated IK,ACh in uninfected and freshly dissociated atrial myocytes but the effect was larger and more consistent in infected myocytes. 3. Pertussis toxin pretreatment (100 ng ml-1 overnight) did not block the effect of isoprenaline. The effect of isoprenaline became persistent if cells were pretreated with cholera toxin (200 ng nl-1). 4. Signal transduction events distal to adenylyl cyclase were not involved in isoprenaline-induced IK,ACh. Forskolin (10 microM) did not activate IK,ACh. Inhibition of adenylyl cyclase with cytoplasmic application of 300 microM 2'-deoxyadenosine 3'-monophosphate did not prevent the activation of IK,ACh by isoprenaline. 5. Cytoplasmic application of a betagamma binding peptide derived from the C terminus of beta-adrenergic receptor kinase 1 (50 microM) prevented the effect of isoprenaline on IK,ACh. The peptide did not prevent the stimulation of the L-type calcium current by isoprenaline. 6. The results indicate that beta-adrenoceptors can activate IK,ACh in atrial myocytes through the release of betagamma subunits from Gs.
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PMID:Isoprenaline can activate the acetylcholine-induced K+ current in canine atrial myocytes via Gs-derived betagamma subunits. 985 23

Endothelins (ETs) are a family of peptide hormones that act on G protein-coupled ET(A) and ET(B) receptors. ETs exert inotropic and chronotropic actions in the heart. Myocardial ischemia is associated with increased plasma levels of ET and cell swelling. We examined the effect of ETs on dog atrial swelling-induced chloride current (I(Cl,swell)). Whole-cell patch clamp was used; 10 nM ET-1 or ET-2 increased I(Cl,swell) by approximately twofold. ET-2 had no effect if I(Cl,swell) activation was prevented by hypertonic superfusate. Outward ET-2-induced current was blocked by 150 microM DIDS more effectively than inward current. Overnight pretreatment with phorbol 12-myristate 13-acetate (1.6 microM), pertussis toxin (100 ng/ml), or dialysis of the cell with 300 microM 2'-deoxyadenosine 3'-monophosphate, a P-site inhibitor of adenylyl cyclase, did not diminish the effect of ET-2. The effect of ET-2 was blocked by an ET(A1)- (BQ123), but not an ET(B)-selective (BQ788) antagonist. ET-2-induced currents were inhibited approximately 70% by PD 98059 (30 microM), a selective MAPK kinase (MEK) blocker. PD 98059 did not affect basal whole cell current or I(Cl,swell) before exposure to ET-2. The data suggest that MEK activity is not required for activation of atrial I(Cl,swell) but that ET-2 stimulates I(Cl,swell) by a MEK-dependent pathway.
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PMID:Cardiac swelling-induced chloride current is enhanced by endothelin. 1081 80

We have examined the expression of mRNA for several P2Y nucleotide receptors by northern blot analysis in purified type 1 cerebellar astrocyte cultures. These results suggest that different P2Y subtypes could be responsible for ATP metabotropic calcium responses in single type 1 astrocytes. To identify these subtypes we have studied the pharmacological profile of ATP calcium responses using fura-2 microfluorimetry. All tested astrocytes responded to ATP and UTP stimulations evoking similar calcium transients. Most astrocytes also responded to 2-methylthioATP and ADP challenges. The agonist potency order was 2-methylthioATP > ADP > ATP = UTP. Cross-desensitization experiments carried out with ATP, UTP, and 2-methylthioATP showed that 2-methylthioATP and UTP interact with different receptors, P2Y(1) and P2Y(2) or P2Y(4). In a subpopulation of type 1 astrocytes, ATP prestimulation did not block UTP responses, and UDP elicited clear intracellular Ca(2+) concentration responses at very low concentrations. 2-MethylthioATP and UTP calcium responses exhibited different sensitivity to pertussis toxin and different inhibition patterns in response to P2 antagonists. The P2Y(1)-specific antagonist N:(6)-methyl-2'-deoxyadenosine 3', 5'-bisphosphate (MRS 2179) specifically blocked the 2-methylthio-ATP responses. We can conclude that all single astrocytes coexpressed at least two types of P2Y metabotropic receptors: P2Y(1) and either P2Y(2) or P2Y(4) receptors. Moreover, 30-40% of astrocytes also coexpressed specific pyrimidine receptors of the P2Y(6) subtype, highly selective for UDP coupled to pertussis-toxin insensitive G protein.
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PMID:Coexpression of several types of metabotropic nucleotide receptors in single cerebellar astrocytes. 1103 96

In the search for P2-receptors modulating the stimulation-evoked entry of calcium at processes of PC12 cells differentiated in the presence of nerve growth factor and neurotrophin-3, electrically evoked increases in free calcium were assessed by fura-2 microfluorimetry. Omission of calcium and addition of cadmium (100 microM) or the N-type calcium channel blocker omega-conotoxin GVIA (0.5 microM) abolished or markedly reduced the evoked responses. The P2Y-receptor agonists 2-methylthio adenosine 5'-diphosphate (2-methylthio-ADP), ADP, and adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS) inhibited the electrically evoked entry of calcium without any changes in basal calcium concentrations. 2-Methylthio-ADP was the most potent agonist. Adenosine, P(1),P(4)-di(adenosine-5')-tetraphosphate (Ap4A), UDP, and UTP (30 microM each) had no effect. The effect of ADPbetaS (30 microM) was abolished by the P2-antagonists reactive blue 2 (3 microM), suramin (100 microM), 2-methylthio-AMP (10 microM), p-chloromercuriphenyl sulfonic acid (1 microM), and AR-C 69931MX [N(6)-(2-methylthioethyl)-2-(3,3,3-trifluoropropylthio)-beta,gamma-dichloromethylene adenosine 5'-triphosphate] (300 nM). In contrast, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (10 microM), the selective P2Y1-receptor antagonist MRS 2179 (N(6)-methyl-2'-deoxyadenosine 3',5'-bisphosphate; 10 microM), as well as the adenosine A(1)-receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine; 100 nM), caused no change. Pretreatment with pertussis toxin abolished the effect of ADPbetaS. Reverse transcriptase-polymerase chain reaction revealed the presence of mRNA for P2Y12-receptors in nondifferentiated and differentiated PC12 cells. The results indicate that processes of differentiated PC12 cells possess P2Y12-receptors coupling to pertussis toxin-sensitive G-proteins and mediating an inhibition of the stimulation-evoked entry of calcium through omega-conotoxin GVIA-sensitive calcium channels. This suggests a role of P2Y12-receptors in neuromodulation in addition to their involvement in platelet aggregation.
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PMID:P2Y-receptors mediating an inhibition of the evoked entry of calcium through N-type calcium channels at neuronal processes. 1238 31


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