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)

In past studies we observed that the chloride channel blocker, diphenylamine-2-carboxylate (DPC) and chemically related drugs (Hoechst compounds 131, 143, 144) inhibited cAMP formation in mouse pituitary tumor cells. The object of this study was to determine whether these drugs inhibited chloride transport in human T-84 colonic carcinoma cells through an effect on cAMP metabolism. Chloride secretion (measured as 125I efflux from isotope-preloaded cells) was stimulated in a concentration-dependent manner by vasoactive intestinal polypeptide (VIP) (EC50 = 1.5 x 10(-10) M) which similarly increased cAMP synthesis (EC50 = 1.6 x 10(-8) M). The cAMP response to VIP was inhibited 17, 52, 55, and 78% maximally by DPC and compounds 144, 143, and 131, respectively. In untreated T-84 cells, 125I secretion fell by 66% after 3 min; VIP (10(-7) M) increased secretion about fivefold over the same period. Both basal and VIP-stimulated 125I secretion were inhibited up to 60% by compound 131. Pretreatment of cells with pertussis toxin did not attenuate the inhibitory effect of channel blockers on either VIP-stimulated cAMP synthesis or 125I secretion. The cationophore, A-23187, which had no effect on cAMP formation, and 8-Br-cAMP both stimulated 125I secretion from T-84 cells. These secretory responses were inhibited by compound 131. The mechanism by which phenylanthranilic acids antagonize cAMP synthesis and its significance is not known; however, the data suggest that this family of drugs may inhibit chloride transport by both cAMP-dependent and independent mechanisms.
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PMID:Antagonists of epithelial chloride channels inhibit cAMP synthesis. 164 53

The roles of carrier and adjuvant in the induction of primary antibody responses to the haptenic drug chlorhexidine (which interacts only electrostatically with proteins) and its N-chlorinated derivative (which binds covalently to proteins) were investigated. N-chloro chlorhexidine, covalently linked to either ovalbumin, KLH, thaumatin, LPS-associated protein or human serum protein, but not autologous mouse serum protein or LPS itself, induced both IgE and IgG anti-chlorhexidine antibody synthesis when injected, with alum adjuvant, into BALB/c mice. Bordetella pertussis (BP) could function as both carrier and adjuvant, but no response was obtained by injection of N-chloro chlorhexidine alone or with alum adjuvant. The immunogenicity of N-chlorinated chlorhexidine was directly related to the degree of its substitution onto the carrier which, in turn, was proportional to the level of chlorine (mM) employed. Chlorine also affected the immunogenicity of the various carriers. In the absence of chlorine, chlorhexidine induced only low level IgG antibody synthesis, but only if presented in a 'pseudoplurivalent' form, as a chlorhexidine-mediated protein precipitate (with alum) or electrostatically bound to a particulate carrier such as BP.
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PMID:Factors influencing the immunogenicity of the haptenic drug chlorhexidine in mice. II. The role of the carrier and adjuvants in the induction of IgE and IgG anti-hapten responses. 379 38

Dibutyryl cAMP-differentiated HL-60 human leukemia cells possess receptors for the chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), C5a and leukotriene B4 (LTB4). We compared the effects of these chemoattractants in HL-60 membranes and in intact HL-60 cells. fMLP, C5a and LTB4 stimulated GTP hydrolysis and guanosine 5'-O-[3-thio]triphosphate (GTP[gamma S]) binding in HL-60 membranes with similar effectiveness and in a pertussis toxin (PTX)-sensitive manner. They also stimulated photolabeling of the alpha-subunits of the guanine nucleotide-binding proteins (G-proteins), Gi2 and Gi3 with similar effectiveness. Chloride salts of monovalent cations differentially enhanced and inhibited chemoattractant-induced GTP hydrolyses. C5a was less effective than fMLP in enhancing cholera toxin-catalysed ADP-ribosylation of Gi alpha 2 and Gi alpha 3, and LTB4 was ineffective. fMLP was more effective than C5a and LTB4 in stimulating Ca2+ influx in HL-60 cells. C5a- and LTB4-induced rises in cytosolic Ca2+ concentration ([Ca2+]i) were PTX-sensitive, whereas the effect of fMLP was partially PTX-insensitive. LTB4-induced rises in [Ca2+]i were more sensitive towards homologous desensitization than those induced by C5a, and the effect of fMLP was resistant in this regard. C5a was considerably less effective than fMLP in activating superoxide anion formation and azurophilic granule release, and LTB4 was ineffective. Our data suggest that fMLP, C5a and LTB4 effectively activate the G-proteins, Gi2 and Gi3, in HL-60 cells and that fMLP may additionally activate PTX-insensitive G-proteins. fMLP, C5a and LTB4 are full, partial and incomplete secretagogues, respectively, and these differences may be due to differences in homologous receptor desensitization and qualitative Gi-protein activation.
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PMID:Differential activation of dibutyryl cAMP-differentiated HL-60 human leukemia cells by chemoattractants. 798 96

Bordetella pertussis suppresses transcription of its virulence genes in response to specific environmental conditions, a response called modulation. The organism responds to high concentrations of SO4 and CIO4 ions, nicotinic acid, and nicotinic acid analogs in vitro; however, the in vivo modulator has not been identified. We investigated which chemical structures of the nicotinic acid molecule are important for modulation by testing various analogs for their ability to modulate. The ring nitrogen of nicotinic acid was not required, since benzoic acid was a modulator. In contrast, the carboxyl group was required, since derivatives like ethylnicotinate, 3-pyridylcarbinol, 3-acetyl pyridine, and 6-chloronicotinamide with altered carboxyl groups were not modulators. The planar ring structure or resonance in the ring was required for modulation, since nipecotic acid failed to modulate. The most potent modulators were nicotinic acid derivatives with electron-withdrawing substituents in the meta or para position relative to the carboxyl group. Relative hydrophilicity of substituents did not appear to contribute to modulation. Although these modulators elicited a clear biological response, the mechanism of modulation remains unclear, because no binding of the modulator 35SO4 or [14C]4-chlorobenzoic acid to whole B. pertussis was detected. However, modulation appears to involve a charge-charge interaction, since the response was blocked by chlorine ions.
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PMID:Characterization of environmental regulators of Bordetella pertussis. 843 1