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)

1. The effects of selective alpha 1- and alpha 2-adrenoceptor agonists and antagonists on the stimulation-induced (S-I) outflow of radioactivity at 2 Hz were investigated in superfused rabbit renal arteries incubated with [3H]-noradrenaline. 2. The alpha 1-adrenoceptor agonist methoxamine (10 microM) inhibited S-I outflow of radioactivity and this effect was abolished by the alpha 1-adrenoceptor antagonist prazosin (0.1 microM) but not by the alpha 2-adrenoceptor antagonist rauwolscine (1 microM). Neither the prostaglandin synthesis inhibitor indomethacin (10 microM) nor the adenosine receptor antagonist 8-phenyl-theophylline (1 microM) prevented the inhibitory effect of methoxamine. 3. The alpha 2-adrenoceptor agonists clonidine (0.1 microM) and UK 14304 (0.1 microM) both inhibited S-I outflow of radioactivity. The inhibitory effect of clonidine was blocked by rauwolscine but not by prazosin. The inhibitory effect of UK 14304 was markedly reduced by rauwolscine. 4. Prazosin (0.1 microM) alone did not enhance the S-I outflow of radioactivity at 2 Hz and slightly enhanced S-I outflow at 4 Hz. Rauwolscine (1 microM) alone markedly enhanced S-I outflow of radioactivity at 2 and 4 Hz. 5. Pretreatment of the arteries with pertussis toxin (1 microgram ml-1) did not significantly alter the inhibitory effects of methoxamine or UK 14304 or the potentiation by rauwolscine. However, pretreatment of the arteries with a higher concentration of pertussis toxin (5 micrograms ml-1) prevented the inhibitory effect of methoxamine but still did not affect the responses to UK 14304 and rauwolscine. 6. Pretreatment of the arteries with N-ethylmaleimide (NEM, 10 microM) for 30 min did not alter the inhibitory effect of methoxamine but markedly attenuated the inhibitory effect of UK 14304 and the facilitatory effect of rauwolscine. 7. The results suggest that both alpha 1- and alpha 2-adrenoceptors take part in the modulation of noradrenaline release from sympathetic nerves in rabbit renal arteries. Alpha 1-adrenoceptor mediated inhibition may be coupled to G-proteins which are pertussis toxin sensitive and alpha 2-adrenoceptor mediated inhibition to G-proteins which are NEM-sensitive.
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PMID:Activation of alpha 1- and alpha 2-adrenoceptors inhibits noradrenaline release in rabbit renal arteries: effects of pertussis toxin and N-ethylmaleimide. 134 90

1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor signal transduction in mouse atria was examined by use of the G-protein inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor partial agonist clonidine (0.03 microM) inhibited the electrical stimulation-induced (S-I) outflow of radioactivity from mouse atria which were incubated with [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.). 3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S-I outflow of radioactivity from mouse atria were significantly less in atria incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]-noradrenaline incubation. 5. The results suggest that prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive, but pertussis toxin insensitive.
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PMID:Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are sensitive to N-ethylmaleimide, but not pertussis toxin. 135 69

Isolated tail arteries from Wistar rats, prelabeled with [3H]norepinephrine (NE) were subjected to electrical field stimulation (24 pulses at 0.4 Hz and 200 mA). Both NE release and vasoconstriction were measured in parallel. The selective alpha 2-adrenoceptor agonist B-HT 933 diminished the evoked NE release in a concentration-dependent manner. This effect of B-HT 933 was counteracted by the selective alpha 2-adrenoceptor antagonist rauwolscine, which given alone enhanced evoked transmitter release, indicating the presence of autoinhibition. N-Ethylmaleimide (NEM) (3 microM), which also in itself increased transmitter release, virtually abolished facilitation of release by 0.1 microM rauwolscine and diminished its inhibition by 10 microM B-HT 933. The diminution of the inhibitory effect of B-HT 933 was even more pronounced when the current strength was decreased from 200 mA to 90 mA to compensate for the NEM-induced increase in transmitter release. Treatment of the arteries with NEM did not affect the perfusion pressure. In contrast, however, the B-HT 933-induced increase in basal perfusion pressure was significantly diminished by NEM. Although 10 microM B-HT 933 given alone did not affect stimulation-evoked vasoconstriction, it caused a significant increase in arteries treated with NEM. In conclusion, the observed NEM-sensitivity of the presynaptic and vascular alpha 2-adrenoceptor mechanisms is compatible with the idea that both pre- and postsynaptic alpha 2-adrenoceptors couple to Pertussis toxin (PTX)-sensitive G proteins.
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PMID:N-ethylmaleimide diminishes alpha 2-adrenoceptor-mediated effects on norepinephrine release in rat tail arteries. 137 19

To examine whether GTP-binding proteins (G proteins) mediate the ability of neurotensin to lower the affinity of dopamine D2 agonist binding, the modulation by neurotensin in vitro of N-[3H]propylnorapomorphine [( 3H]-NPA) binding was investigated following pretreatment with pertussis toxin and N-ethylmaleimide in rat neostriatal membranes. Preincubation with N-ethylmaleimide (100 microM) markedly inhibited pertussis toxin-induced back-ADP ribosylation of three proteins with apparent molecular masses of 41, 40, and 39 kDa, respectively. This inhibition was prevented by adding dithiothreitol (250 microM) during the preincubation. N-Ethylmaleimide increased the KD (180 +/- 30%) and decreased the Bmax (-31 +/- 9%) of [3H]NPA binding sites but did not affect the binding properties of the selective D2 antagonist [3H]raclopride. N-Ethylmaleimide pretreatment did not affect the neurotensin (3 nM)-induced increase in the KD of [3H]NPA binding sites. Pertussin toxin treatment in vivo and in vitro was similarly ineffective. In conclusion, the present study indicates that neurotensin modulation of D2 agonist binding in neostriatal membranes is not mediated by G proteins.
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PMID:Neurotensin decreases the affinity of dopamine D2 agonist binding by a G protein-independent mechanism. 182 79

The possibility that the terminal serotonin (5-HT) autoreceptor in the rat hippocampus is coupled to Gi, Go or Gs regulatory proteins was investigated using the electrically evoked overflow of [3H]5-HT from preloaded slices. Pertussis toxin, which inactivates Gi/o or cholera toxin, which stimulates Gs, was injected directly in the hippocampus 3 to 11 days prior to the experiments. Hippocampus slices were prepared, loaded with [3H]5-HT, superfused continuously, and stimulated electrically 72 min (S1) and 116 min (S2) after the beginning of superfusion. In the absence of any drug, the evoked overflow of [3H]5-HT in S1 was not altered by either toxin. The enhancing effect of the 5-HT reuptake blocker paroxetine (1 mumol/l) on the evoked [3H]5-HT overflow was also unaltered by these toxins. 5-Carboxyamidotryptamine, a 5-HT autoreceptor agonist, inhibited in a concentration-dependent manner the stimulation-evoked release of [3H]5-HT. The concentration-effect curve (0.001-0.1 mumol/l) for this drug was not altered by pretreatment with either pertussis or cholera toxin. Similarly, the effect of another 5-HT autoreceptor agonist, 5-methoxytryptamine (0.1 and 1 mumol/l), was not altered in the pretreated rats. In addition, the reduction of [3H]5-HT overflow obtained by increasing the stimulation frequency from 1 Hz to 5 Hz, which is due to an increase in terminal 5-HT autoreceptor activation at the higher frequency, was not altered by either toxin. The enhancing effect of the 5-HT autoreceptor antagonist methiothepin (1 mumol/l) on stimulation-evoked [3H]5-HT overflow was not changed by either pretreatment. N-Ethylmaleimide inactivates Gi/o proteins by alkylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Terminal serotonin autoreceptor function in the rat hippocampus is not modified by pertussis and cholera toxins. 194 10

1. The amphiphilic peptide mastoparan is known to affect phosphoinositide breakdown, calcium influx, and exocytosis of hormones and neurotransmitters and to stimulate the GTPase activity of guanine nucleotide-binding regulatory proteins. Another amphiphilic peptide, adenoregulin was recently identified based on stimulation of agonist binding to A1-adenosine receptors. 2. A comparison of the effects of mastoparan and adenoregulin reveals that these peptides share many properties. Both stimulate binding of agonists to receptors and binding of GTP gamma S to G proteins in brain membranes. The enhanced guanyl nucleotide exchange may be responsible for the complete conversion of receptors to a high-affinity state, complexed with guanyl nucleotide-free G proteins. 3. Both peptides increase phosphoinositide breakdown in NIH 3T3 fibroblasts. Pertussis toxin partially inhibits the phosphoinositide breakdown elicited by mastoparan but has no effect on the response to adenoregulin. N-Ethylmaleimide inhibits the response to both peptides. 4. In permeabilized 3T3 cells, both adenoregulin and mastoparan inhibit GTP gamma S-stimulated phosphoinositide breakdown. Mastoparan slightly increases basal cyclic AMP levels in cultured cells, followed at higher concentrations by an inhibition, while adenoregulin has minimal effects. 5. Both peptides increase calcium influx in cultured cells and release of norepinephrine in pheochromocytoma PC12 cells. The calcium influx elicited by the peptides in 3T3 cells is not markedly altered by N-ethylmaleimide. 6. Multiple sites of action appear likely to underlie the effects of mastoparan/adenoregulin on receptors, G proteins, phospholipase C, and calcium.
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PMID:Effects of the amphiphilic peptides mastoparan and adenoregulin on receptor binding, G proteins, phosphoinositide breakdown, cyclic AMP generation, and calcium influx. 784 73

The wasp venom, mastoparan (MP), activates reconstituted pertussis toxin (PTX)-sensitive G-proteins in a receptor-independent manner. We studied the effects of MP and its analogue, mastoparan 7 (MP 7), on G-protein activation in HL-60 cells and a reconstituted system and on nucleoside diphosphate kinase (NDPK)-catalysed GTP formation. MP activated high-affinity GTP hydrolysis in HL-60 membranes with an EC50 of 1-2 microM and a maximum at 10 microM. Unlike the effects of the formyl peptide receptor agonist, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), on GTPase, those of MP were only partially PTX-sensitive. MP-induced rises in cytosolic Ca2+ concentration and superoxide-anion formation in intact HL-60 cells were also only incompletely PTX-sensitive. N-Ethylmaleimide inhibited MP-stimulated GTP hydrolysis to a greater extent than that stimulated by fMet-Leu-Phe. Unlike the latter, MP did not enhance incorporation of GTP azidoanilide into, and cholera toxin-catalysed ADP-ribosylation of, Gi-protein alpha-subunits in HL-60 membranes. By contrast to fMet-Leu-Phe, MP did not or only weakly stimulated binding of guanosine 5'-[gamma-thio]triphosphate to Gi-protein alpha-subunits. MP 7 was considerably more effective than MP at activating the GTPase of reconstituted Gi/G(o)-proteins, whereas in HL-60 membranes, MP and MP 7 were similarly effective. MP and MP 7 were similarly effective at activating [3H]GTP formation from [3H]GDP and GTP in HL-60 membranes and by NDPK purified from bovine liver mitochondria. Our data suggest the following: (1) MP activates Gi-proteins in HL-60 cells, but (2) the venom does not simply mimic receptor activation. (3) MP and MP 7 may activate GTP hydrolysis in HL-60 membranes indirectly through interaction with NDPK. (4) MP 7 is a more effective direct activator of PTX-sensitive G-proteins than MP, whereas with regard to NDPK, MP and MP 7 are similarly effective.
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PMID:Mastoparan may activate GTP hydrolysis by Gi-proteins in HL-60 membranes indirectly through interaction with nucleoside diphosphate kinase. 799 71

Immunochemical detection of pertussis toxin-sensitive guanine-nucleotide binding proteins has been suggested to represent the most direct approach to quantitate the protein than pertussis toxin-catalysed [32P]ADP-ribosylation. The latter technique is potentially hampered by pre-existing covalent modification of the C-terminus. However, limited data exist as to whether and in what way modifications of the C-terminus affect immunoreactivity of Gi alpha (alpha-subunit of the inhibitory G-protein of adenylyl cyclase). Membranes from human myocardium, thrombocytes, adipose tissue and lung were treated with pertussis toxin or N-ethylmaleimide. Both, conditions prevented high affinity agonist binding to m-cholinoceptors and inhibited [32P]ADP-ribosylation by pertussis toxin consistent with the notion that the modifications took place at the C-terminus. Pertussis toxin treatment increased immunoreactivity to different antisera raised against the C-terminal decapeptide of transducin alpha (KENLKDCGLF, DS 1-4, AS). N-Ethylmaleimide reduced immunoreactivity towards all antisera studied. Pertussis toxin reduced the mobility of Gi alpha on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) depending on the presence of the toxin and sensitivity to inhibition of ADP-ribosylation by nicotinamide. In native membranes from none of the tissues studied, immunoreactive material comigrating with pertussis toxin-modified form of Gi alpha was detected. It is concluded that modification of the C-terminus by pertussis toxin or N-ethylmaleimide resulting in the same functional consequence, i.e. prevention of high affinity agonist receptor binding, is capable of producing opposite changes of immunoreactivity. Pertussis toxin treatment reduces the electrophoretic mobility on SDS-PAGE. Separation of the native and pertussis toxin-modified form of Gi alpha on SDS-PAGE demonstrates that endogenously ADP-ribosylated Gi alpha is lacking in membranes from human myocardium, thrombocytes, lung and adipose tissue.
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PMID:C-terminal modifications of pertussis toxin-sensitive G-protein alpha-subunits differentially affect immunoreactivity. Evidence against endogenous ADP-ribosylation in human heart, lung, thrombocytes and adipose tissue. 827 48

4,4'-Diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) stimulates human platelets via alpha 2A-adrenergic receptor-mediated activation of protein kinase C (PKC) independent of the phospholipase C pathway. Here we show, that in permeabilized platelets activation of PKC by DIDS (20 microM), measured as 32P incorporation in pleckstrin, is completely inhibited by guanosine 5'-(2-O-thio)diphosphate (200 microM), an inhibitor of heterotrimeric G-proteins. Also pertussin toxin (4 micrograms/ml), which ADP-ribosylates the alpha-subunits of Gi's and Go, prevents pleckstrin phosphorylation by DIDS. N-Ethylmaleimide (50 microM), which uncouples Gi from alpha 2A-adrenoceptors, inhibits pleckstrin phosphorylation by DIDS in intact platelets. Activation of PKC by 55 nM phorbol 12-myristate 13-acetate and 500 nM platelet-activating factor are not disturbed by NEM. DIDS inhibits by 40 +/- 5% (n = 4) the pertussis toxin-catalyzed [32P]ADP-ribosylation of a 41 kDa protein fraction previously shown to contain the alpha-subunits of Gi alpha-1, Gi alpha-2 and Gi alpha-3. Thus, the alpha 2A-adrenergic receptor activates PKC via a G-protein of the Gi-family.
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PMID:Alpha 2A-adrenergic receptors activate protein kinase C in human platelets via a pertussis toxin-sensitive G-protein. 831 82

[3H]Acetylcholine release elicited with 360 pulses/3 Hz from slices of rabbit hippocampus is facilitated in the presence of the muscarine (M) receptor antagonist atropine (indicating the existence of autoinhibition) and diminished by the M receptor agonists carbachol and oxotremorine. N-Ethylmaleimide (30 microM) and pertussis toxin (8 micrograms/ml) counteracted antagonist-induced facilitation and agonist-induced inhibition of release, suggesting that a pertussis toxin-sensitive GTP-binding protein is involved in the chain of events mediating activation of M receptors to inhibition of release. Neither 8-bromo-cyclic AMP (300 microM), a membrane analogue of cyclic AMP, nor rolipram (10 microM), a phosphodiesterase inhibitor, affected electrically evoked release of [3H]acetylcholine. They also did not influence the oxotremorine-induced inhibition of transmitter release. In conclusion, no evidence was found for the assumption that activation of M autoreceptors is linked to inhibition of adenylate cyclase.
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PMID:Muscarine receptors regulating electrically evoked release of acetylcholine in hippocampus are linked to pertussis toxin-sensitive G proteins but not to adenylate cyclase. 836 Jun 71


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