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)

Pertussis toxin may inactivate N proteins linked to phospholipase C. We examined the effect of pretreatment with pertussis toxin at different concentrations and times on agonist-induced PGE2 synthesis in mesangial cells. Two to four hours with 10-50 ng/ml of pertussis toxin inhibited the response to angiotensin and platelet activating factor, but with a different sensitivity. This was associated with decreased [14C]arachidonic acid release in prelabeled cells. The response to A23187 was unaltered. At high concentrations (1 to 5 micrograms/ml) pertussis toxin increased basal PGE2 and the response to all agonists. Pertussis toxin pretreatment resulted in a dose-dependent ribosylation of a 40 kDa protein band. Thus, responses to different agonists have different sensitivity to pertussis toxin inhibition, which at high concentrations may even have opposite effects.
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PMID:Different concentrations of pertussis toxin have opposite effects on agonist-induced PGE2 formation in mesangial cells. 309 83

Prostaglandin E1 and E2 (PGE) antagonize the phosphaturic effect of parathyroid hormone (PTH), but do not alter the phosphaturia evoked by adenosine 3',5'-cyclic monophosphate (cAMP) analogues. These findings support the idea that PGE interfere with activation of adenylate cyclase in the renal proximal tubule. We tested this hypothesis in the rabbit renal proximal straight tubule (PST). In the PST, adenylate cyclase was activated by PTH (Km = 10(-9) M PTH), but not by PGE2, which attenuated the activation of adenylate cyclase by PTH. The inhibition by PGE2 of PTH action was prevented by pertussis toxin, which deactivates the regulatory aggregate, Ni. In the PST, PGE2 also attenuated the activation of adenylate cyclase by cholera toxin. The inhibitory effect of PGE2 was selective; PGE2 did not inhibit activation of adenylate cyclase in glomeruli, but it inhibited the enzyme in proximal convoluted tubules (PCT) and PST. We conclude that PGE2 inhibits adenylate cyclase in rabbit proximal tubule. We propose that this action may, in part, regulate transport function in vivo.
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PMID:Prostaglandin E2 is an inhibitor of adenylate cyclase in rabbit proximal tubule. 316 52

Prostaglandin E2 (PGE2) and 16,16-dimethyl PGE2 were found to inhibit a hepatic glycogenolysis stimulated by epinephrine in the presence of propranolol (alpha 1-adrenergic response), isoproterenol (beta-adrenergic response) and glucagon in primary cultures of rat hepatocytes. The inhibitory effects to these stimulations were maximally increased (60-100%) in the cultures on day 2 or 3. Pretreatment of the cultured hepatocytes with pertussis toxin (islet-activating protein) resulted in a complete blockage of the prostaglandin-induced inhibition of glycogenolysis in a dose-dependent manner. Pertussis toxin had no significant effect on the glycogenolysis stimulated by these compounds in the absence of prostaglandin. The data suggest that the hepatic glycogenolysis stimulated by alpha 1- and beta-adrenergic responses and glucagon are modulated by the E series of prostaglandins via pertussis toxin-sensitive guanine nucleotide regulatory protein.
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PMID:Pertussis toxin blocks an inhibition of hormone-stimulated glycogenolysis by prostaglandin E2 and its analogue in cultured hepatocytes. 323 2

The time course of the inflammatory reaction in the rat air pouch model of synovial inflammation has been investigated at different stages of development of the lining structure using immune (pertussis vaccine) and non-immune (carrageenan) irritants. Exudate volumes and leucocyte numbers were greater with carrageenan than with pertussis vaccine but with both irritants much greater reactions were obtained when the irritant was injected at a time when the air pouch architecture most closely resembled synovium (i.e. 6 days). The time course of fluid accumulation following carrageenan in 6 day pouches was not interrupted when exudate was aspirated from the pouch six days after carrageenan injection. In the 6 day old air pouch PGE2 and 6-oxo-PGF1 alpha concentration peaked at 6 hours and 24 hours respectively. With carrageenan and pertussis vaccine stimulation, LTB4 concentrations were maximal at 3-6 hours with both irritants and low concentrations were still present at 13 days. The presence of a lining structure was found to influence concentrations of PGE2 in the air pouch. Pre-treatment with colchicine or 5-fluorouracil to reduce cell accumulation was not found to effect the modified PGE2 response. Our findings suggest that the presence of a synovial like lining structure may induce changes in composition in respect to cellular content and in putative mediator concentrations. We conclude that it is important in elucidating the mechanisms involved in arthritic inflammation to study injury in a cavity lined by macrophages and fibroblasts.
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PMID:Studies of eicosanoid production in the air pouch model of synovial inflammation. 346 70

The effects of 16(S)-methyl-20-methoxy-PGE2 (YPG-209) on hypersensitivity reactions were investigated in the rat, guinea-pig and mouse. Intravenously administered YPG-209 was 150 times as potent as disodium cromoglycate (DSCG) in the inhibitory effect on the IgE(mouse)-mediated 24 hr rat PCA. When administered intravenously to guinea-pigs, YPG-209 inhibited significantly the IgE (guinea-pig)-mediated 8 day guinea-pig PCA, whereas DSCG exhibited no significant inhibitory effects. The oral doses of YPG-209 diminished both histamine and 5-hydroxytryptamine hypersensitivity of the Bordetella pertussis-treated mice. These results suggest that YPG-209 exhibits not only the prevention of mediator release but also the antimediator effect in laboratory animals.
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PMID:Inhibition of hypersensitivity reactions by 16(S)-methyl-20-methoxy-PGE2 (YPG-209) in animals. 625 64

There is evidence to suggest that PGE2 plays an important role in the regulation of vascular smooth muscle tone. To determine the cellular basis of this action, we studied the effect of PGE2 on force in helical muscle strips from rat tail artery. PGE2 evoked a sustained contractile response. The contractile response was concentration-dependent, with an EC50 value of 9.6 microM. Patch-clamp studies were conducted to investigate the effects of PGE2 on K channels in isolated vascular smooth muscle cells from rat tail artery. Current-clamp studies showed that PGE2 (1 microM) depolarized the membrane by 15.9 +/- 1.3 mV. Under voltage-clamp conditions, a voltage-dependent, delayed outward rectifier K current was generated by stepwise depolarization from a holding potential of -80 mV. The current, which was activated at -45 to -40 mV and showed almost no inactivation, was inhibited by 45% using 10 mM TEA. PGE2 inhibited the outward K current in a concentration-dependent manner, with EC50 values of 3.5 microM and 4.9 microM in primary and subcultured cells, respectively. The PGE2 receptor antagonist sodium meclofenamate abolished the PGE2-induced K current inhibition. Furthermore, the intracellular application of guanosine 5'-O(-)[2-thiodiphosphate] (GDP beta S), a G protein inhibitor, and pretreatment of the cells with cholera toxin prevented the PGE2-induced inhibition, whereas application of pertussis toxin did not.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin E2 contracts vascular smooth muscle and inhibits potassium currents in vascular smooth muscle cells of rat tail artery. 747 58

We have previously shown that norepinephrine can produce hyperalgesia via an alpha 2-adrenergic receptor mechanism. The alpha 2-adrenergic receptor agonist clonidine has, however, also been shown to produce peripheral analgesia. In view of the multiple alpha 2-subtypes currently known (i.e. alpha 2A, alpha 2B and alpha 2C), we evaluate the alpha 2-receptor subtypes mediating norepinephrine-induced peripheral hyperalgesia and clonidine analgesia. Norepinephrine and the alpha 2-adrenergic agonists clonidine and UK 14,304 (1-1000 ng), when co-injected with the calcium ionophore A23187 (1000 ng) produced dose-dependent hyperalgesia in the Randall-Selitto paw withdrawal test. Norepinephrine (100 ng) hyperalgesia was dose-dependently antagonized by alpha 2-adrenergic receptor antagonists. From the estimated ID50, the rank order of potency was: SK&F 104856 (alpha 2B) approximately imiloxan (alpha 2B) > rauwolscine (alpha 2C) >> BRL 44408 (alpha 2A). Norepinephrine hyperalgesia was not significantly affected by pertussis-toxin treatment. Prostaglandin E2 (100 ng) hyperalgesia was inhibited dose-dependently, by clonidine and UK 14,304. Rauwolscine was more potent in reversing the inhibitory effect of clonidine on prostaglandin E2 than imiloxan while BRL 44408 was ineffective. The inhibitory effect of clonidine on prostaglandin E2 hyperalgesia was reversed by pertussis toxin. These data suggest that alpha 2B-subtype receptors mediate (norepinephrine hyperalgesia while the antinociceptive effect of alpha 2-agonist is mediated by the alpha 2C-subtype receptor. Differential coupling of these receptor subtypes to second messenger systems and location on different cell types in the rat paw may explain, at least in part, their differential responses to alpha 2-agonist stimulation, leading to hyperalgesia and analgesia.
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PMID:Peripheral nociceptive effects of alpha 2-adrenergic receptor agonists in the rat. 747 83

Decreased airway relaxation to beta-adrenoceptor stimulation has been hypothesized as a potential mechanism leading to enhanced bronchoconstrictor responsiveness in asthma. In addressing potential mechanisms underlying this phenomenon, the relative contributions of beta-adrenoceptor-coupled transmembrane signaling mechanisms were examined in isolated rabbit tracheal smooth muscle (TSM) passively sensitized with serum from atopic asthmatic patients and in TSM comparably exposed to non-atopic (control) human serum. During half-maximal isometric contraction of the tissues with acetylcholine, relative to control TSM, the sensitized tissues exhibited significant attenuation of both their maximal relaxation (Rmax) and sensitivity (i.e., -log 50% Rmax) to cumulative administration of isoproterenol (P < 0.001) or prostaglandin (PG)E2 (P < 0.001). In contrast, the relaxation responses to forskolin, a diterpene that directly activates adenylate cyclase, were similar in both tissue groups. Extended studies demonstrated that the attenuated relaxation to isoproterenol and PGE2 in sensitized TSM was 1) ablated by pretreatment with the muscarinic M2-receptor antagonists methoctramine (10(-6) M) or gallamine (10(-4) M); 2) also inhibited by pretreatment with pertussis toxin (100 ng/ml), which ADP ribosylates the inhibitory G protein (G(i)) negatively coupled to adenylate cyclase activation; and 3) associated with diminished adenosine 3',5'-cyclic monophosphate accumulation in response to isoproterenol administration. Moreover, based on Western immunoblot analysis, we found that G(i) protein expression was increased in membrane fractions from sensitized TSM, related to enhanced expression of the G(i) alpha 3 subunit. Collectively, these observations provide new evidence that the impaired beta-adrenoceptor-mediated relaxation in atopic sensitized airways is associated with increased muscarinic M2 receptor/G(i) protein-coupled expression and function.
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PMID:Mechanism of impaired beta-adrenoceptor responsiveness in atopic sensitized airway smooth muscle. 749 84

The group of prostaglandin (PG) E2- and prostacyclin receptors consists of different subtypes, which exhibit different affinities for prostaglandins and synthetic analogues. PGE2 activities the E-type PG receptor subtypes EP1, EP2 and EP3, whereas the PGE2 analogue, sulprostone, binds only to the EP1 and EP3 receptor subtypes. The stable PGI2 analogues, iloprost and cicaprost, both activate the PGI2 receptor (IP) and iloprost, additionally, bind to the EP1 subtype. Using these subtype-selective PG receptor agonists, we studied the interaction of PG receptor subtypes with Gs and Gi-type heterotrimeric guanine nucleotide-binding proteins (G proteins) in membranes from the human erythroleukaemia cell line, HEL. Sulprostone stimulated high-affinity GTPase in HEL membranes in a pertussis toxin (PTX)-sensitive manner. In contrast, the stimulations induced by PGE2, iloprost and cicaprost were only partially inhibited by PTX. PGE2, sulprostone, iloprost and cicaprost stimulated cholera toxin-catalysed ADP-ribosylation as well as labelling with GTP azidoanilide of membrane proteins comigrating with immunologically identified Gi protein alpha subunits. Furthermore, PGE2, iloprost and cicaprost enhanced GTP azidoanilide-labelling of Gs protein alpha subunits, whereas sulprostone did not. We suggest that in HEL cells (1) EP1 and EP3 receptor subtypes activate G1 proteins, that (2) the EP2 receptor subtype activates Gs proteins and that (3) the IP receptor activates both Gi and Gs proteins.
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PMID:Differential activation of Gi and Gs proteins by E- and I-type prostaglandins in membranes from the human erythroleukaemia cell line, HEL. 753 11

Incorporation of myo-[2-3H]-inositol into peripheral blood mononuclear cells (PBMNC) and T-cell enriched lymphocytes was evaluated in in-vitro experiments in chronic renal failure (CRF) patients and healthy subjects. Incorporation of myo-[2-3H]-inositol into the cells of CRF patients on conservative and haemodialysis treatment was found to be impaired in comparison with that observed in normal cells. Following PHA stimulation of the cells of CRF patients myo-[2-3H]-inositol incorporation decreased even further, while it increased in normal cells. Five-hour haemodialysis session significantly depressed myoinositol incorporation into PBMNC, while its incorporation into T-cell enriched lymphocytes remained unaffected. Myoinositol incorporation into PBMNC and T-cell enriched lymphocytes was inhibited by prostaglandins and leukotrienes and was inversely related to the extent of pertussis toxinsensitive G protein activation. Reduced myoinositol incorporation into uraemic PHA-stimulated PBMNC may depend at least in part on their enhanced PGE2 and LTB4 release accompanied by increased intracellular cAMP production. In CRF impaired myoinositol incorporation into immune cells may prove the disarrangement in the early events of transmembrane signal transduction, which may share the responsibility for the cell-mediated immune defect in these patients.
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PMID:Myoinositol incorporation into lymphocytes of chronic renal failure patients is impaired. 756 75


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