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

1. The membrane currents evoked by glutamate agonists on isolated and identified neurones of molluscan pedal ganglia were investigated using the voltage clamp technique. 2. The fast chloride current (Er (reversal potential) = -41 mV) evoked in a Ped-9 neurone by application of glutamate, quisqualate and ibotenic acid could be blocked by furosemide (0.1 mM). The slow potassium current (Er = -85 mV) evoked in Ped-8 and Ped-9 neurones by glutamate, quisqualate and kainate could be blocked by tetraethylammonium (50 microM). 3. N-Methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) failed to induce a response in neurones studies. 4. The spider venoms argiopine and argiopinine III (50-500 nM) selectively inhibited quisqualate-induced potassium current, but had no influence on glutamate-, ibotenate- or quisqualate-induced chloride and kainate-induced potassium currents. Glutamate-induced potassium current was partially inhibited by argiopine and argiopinine III. 5. The existence of several types of distinct glutamate receptors was confirmed in cross-desensitization experiments, and a lack of interaction was observed between quisqualate and kainate. 6. Potassium currents induced both by quisqualate and kainate strongly depended on temperature and could be blocked by pertussis toxin. Intracellular injection of the calcium chelator, EGTA, did not affect quisqualate and kainate responses. 7. In neurones loaded with non-hydrolysable GTP analogues, GTP-gamma-S (guanosine-5'-O-(3-thio)triphosphate) or GppNHp (5'-guanylylimidodiphosphate), the potassium current was gradually induced in the absence of agonists. As this current progressed, the magnitude of the glutamate- or kainate-evoked current transients became smaller and finally negligible. The GTP-gamma-S-induced current was not inhibited by argiopine. 8. These data indicate that in the molluscan neurones studied there are at least three pharmacologically distinct glutamate receptors: (1) a receptor of quisqualate-ibotenate type which directly controls chloride channel; (2) quisqualate and (3) kainate receptors which control in calcium-independent manner the common potassium channel by activation of GTP-binding protein.
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PMID:Different types of glutamate receptors in isolated and identified neurones of the mollusc Planorbarius corneus. 165 12

Elevation of cellular cyclic AMP by agents such as isoproterenol plus 3-isobutyl-1-methylxanthine produced rapid and reversible dendritic formation of bovine pulmonary artery endothelial cells in the monolayer. The effect did not occur with exposure of the cells to a variety of other vasoactive agents, calcium ionophore, phorbol ester, or cyclic GMP. The cyclic AMP-induced configurational change was completely inhibited by 2.5 mM N-phenylanthranilic acid or 145 mM sodium gluconate (Cl- channel inhibitors) and was partially inhibited by 2.5 mM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), but it was not affected by deprivation of Ca2+ or Na+ ion, 1 mM bumetanide (Cl- cotransport inhibitor), 1 mM amiloride (Na+/H+ exchange inhibitor), 0.1 mM verapamil (Ca2+ channel inhibitor), or 5 mM BaCl2 (K+ channel inhibitor), by change in cellular pH, or by pertussis toxin. Trifluoperazine (calmodulin inhibitor, 50 microM), 1 mM EGTA plus 100 microM 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8, intracellular Ca2+ antagonist), and 5 microM cytochalasin B also produced cellular retraction, but these changes were not blocked by chloride channel inhibition. In the presence of 0.1 mM ouabain plus 0.1 mM bumetanide, 36Cl- uptake was decreased by isoproterenol plus isobutylmethylxanthine while its efflux was enhanced. N-Phenylanthranilic acid inhibited the stimulated efflux. We conclude that cyclic AMP induces a configurational change of endothelial cells that is related to Cl- efflux from the cells; the cellular effects may play a role in vascular function.
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PMID:Chloride efflux in cyclic AMP-induced configurational change of bovine pulmonary artery endothelial cells. 169 Jun 13

The effect of several chemically related chloride channel blocking drugs was investigated on the adrenocorticotropic hormone (ACTH) secretory process in mouse clonal AtT-20 corticotrophs. When cells were simultaneously exposed to diphenylamine-2-carboxylate (DPC) or related substances (Hoechst compounds 131, 143, and 144) and the adenylate cyclase activator forskolin, ACTH secretion was inhibited by 76-95% [half-maximal inhibitory concentration (IC50) 450, 15, 84, and 32 microM, respectively]. All four compounds also blocked forskolin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) synthesis in AtT-20 cells by 51-87% (IC50 190, 29, 100, and 130 microM for DPC and compounds 131, 143, and 144, respectively). Pertussis toxin pretreatment of cells caused a partial reversal of DPC-inhibited forskolin-stimulated cAMP formation. The toxin had no effect on inhibition of forskolin-stimulated ACTH secretion by DPC. Secretion of ACTH in response to cAMP-independent stimulants such as the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate or the calcium channel agonist BAY K 8644 were blocked by compound 131 as was the secretory response to 8-bromoadenosine 3',5'-cyclic monophosphate. These results suggest that phenylanthranilic acids have adenylate cyclase inhibiting action but that the postcyclase activity is more relevant to the ability of these compounds to block ACTH secretion. DPC also blocked 125I efflux (an index of Cl- secretion) from AtT-20 cells. Because an increase in osmotic strength of the culture media reduced forskolin-stimulated ACTH secretion, these data suggest that DPC and related compounds may negatively modulate chloride-dependent osmotically driven ACTH secretion from AtT-20 cells.
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PMID:Chloride channel blockers inhibit ACTH secretion from mouse pituitary tumor cells. 170 5

This study examined the electrophysiological responses to antigen and to various stimuli in jejunal mucosa from rats sensitized to egg albumin with alum and pertussis adjuvants. Luminal antigen caused an immediate increase in short-circuit current, a measure of net ion transport, which was one of three different patterns. All were inhibited by the chloride channel blocker diphenyl-2-carboxylate, by chloride-free buffer, and by doxantrazole, a mast cell stabilizer. Depending on the pattern, the histamine-1 antagonist diphenhydramine, the 5-hydroxytryptamine-2 antagonist ketanserin, and the cyclooxygenase inhibitor piroxicam also reduced the responses. A neural component was indicated by inhibition of the responses to luminal antigen by the neurotoxin tetrodotoxin and by neonatal capsaicin treatment, which depletes substance P-containing nerves. In the absence of antigen, histamine and substance P caused increases in short-circuit current; the magnitude of these changes was significantly greater in tissues from sensitized animals than in controls. These data suggest that sensitization itself may result in hypersecretory responses to some inflammatory mediator and neurotransmitter substances.
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PMID:Allergic reactions of rat jejunal mucosa. Ion transport responses to luminal antigen and inflammatory mediators. 234 44

The technique of radiotracer 36Cl- influx in primary culture of rat cerebellar granule cells was applied to study the mechanism of inactivation of the GABAA receptor-activated chloride channel. During sustained application of GABA, muscimol and THIP the specific bicuculline-sensitive 36Cl- influx tends to decline with time. The sequence in decay half-time is GABA less than muscimol less than THIP. Diazepam accelerates the rate of decay of the peak response to GABA. (-)-Baclofen enhances the rate of decline of the response to muscimol in a dose-dependent manner. Treatment of the cells with pertussis toxin antagonized the effect of (-)-baclofen. It is concluded that rat neonatal cerebellar neurons maintained in tissue culture exhibit complex inactivation of the GABAA channel, indicating some interaction with the GABAB receptor system.
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PMID:36Cl- flux measurements on GABAA receptor-activated chloride exchange. Multiple mechanisms of the chloride channel inactivation. 254 12

Glutamate evoked pertussis toxin-sensitive currents in Xenopus oocytes expressing metabotropic glutamate receptor subtype 1 (mGluR1) and exogenous Gi1 alpha. The mGluR1-currents were completely blocked by U-73122, a phospholipase C (PLC) inhibitor and by niflumic acid, a chloride channel blocker. In the oocyte further coinjected with poly(A)+ RNA from the guinea pig cerebellum, the mGluR1-currents were inhibited by U-50488H, an opioid kappa-agonist, and this inhibition was blocked by norbinaltorphimine, an opioid kappa-antagonist. These findings suggest that the mRNA encoding a novel subtype of opioid kappa-receptor which inhibits Gi1-PLC-mediated currents is present in guinea pig cerebellar poly(A)+ fractions.
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PMID:Evidence for a metabostatic opioid kappa-receptor inhibiting pertussis toxin-sensitive metabotropic glutamate receptor-currents in Xenopus oocytes. 749 99

Three different GABA-insensitive Cl- channels could be resolved in cultured hippocampal neurons using the inside-out patch clamp configuration. The most commonly observed channel revealed an inward rectification with a chord conductance of 40 pS in symmetrical Cl- solutions at a membrane potential of -50 mV and had voltage sensitive gating kinetics. Channel openings were not observed in cell-attached patch, and after excision, several minutes of perfusion of the cytoplasmic side were required before detecting the first openings. The open state probability was increased by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S 10(-4) M) and reduced by guanosine 5'-O-(2-thiophosphate) (GDP-beta-S 10(-4) M) suggesting its regulation by G proteins. This new identified chloride channel may account for the previously described voltage-sensitive, inward-rectifying whole cell Cl- current which was enhanced by adenosine in a pertussis toxin-sensitive manner.
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PMID:GTP- and GDP-analogues modulate an inwardly rectifying chloride channel in cultured hippocampal neurons. 771 38

Parathyroid hormone (PTH) raises cytosolic Ca2+ concentration ([Ca2+]i) in isolated or cultured renal proximal tubule cells. The pathways through which this action is mediated are not fully delineated. This study explored these pathways utilizing fura 2. [Ca2+]i of freshly prepared renal proximal tubular cells increased from 150 +/- 3.6 to 281 +/- 9.0 nM after the exposure to 10(-7) M angiotensin II, which served as a positive control. Both PTH-(1-84) and PTH-(1-34) produced a dose-dependent rise in [Ca2+]i. The effects of both moieties were similar up to 10(-7) M, but with higher doses the rise in [Ca2+]i with PTH-(1-84) was greater (P < 0.01) than with PTH-(1-34). This effect of the hormone occurred in the presence or absence of calcium in the media, but the rise in [Ca2+]i was significantly greater in the presence of calcium. The PTH-induced rise in [Ca2+]i was markedly inhibited by PTH antagonist [Nle8,18,Tyr34]bPTH-(7-34)-NH2 (bPTH is bovine PTH), verapamil, or nifedipine. 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, increased [Ca2+]i of cells, but its effect was less than PTH. Staurosporine abolished the TPA effect and partially inhibited that of PTH. A G protein activator raised [Ca2+]i, whereas a G protein inhibitor and pertussis toxin partially blocked the effect of PTH. Sodium or chloride channel blockers or sodium-free media did not modify the effect of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathways involved in PTH-induced rise in cytosolic Ca2+ concentration of rat renal proximal tubule. 786 74

Available data indicate that the liver is a target organ for parathyroid hormone (PTH) and that this effect is most likely mediated by PTH-induced calcium entry into hepatocytes. The present study examined the effects of both PTH-(1-84) and its amino-terminal fragment [PTH-(1-34)] on cytosolic calcium concentration ([Ca2+]i) of hepatocytes and explored the cellular pathways that mediate this potential action of PTH. Both moieties of PTH produced a dose-dependent rise in [Ca2+]i, but the effect of PTH-(1-84) was greater (P < 0.01) than an equimolar amount of PTH-(1-34). This effect required calcium in the medium and was totally [PTH-(1-34)] or partially [PTH-(1-84)] blocked by PTH antagonist ([Nle8,18,Tyr34]bPTH-(7-34)-NH2] and by verapamil or nifedipine. Sodium or chloride channel blockers did not modify this effect. 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), and G protein activator also produced a dose-dependent rise in [Ca2+]i. Staurosporine abolished the effect of TPA, and both staurosporine and calphostin C partially inhibited the effect of PTH. Staurosporine and verapamil together produced greater inhibition of PTH action than each alone. Rp-cAMP, a competitive inhibitor of cAMP binding to the R subunit of protein kinase A, and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a protein kinase A inhibitor, blocked the effect of both DBcAMP and PTH, but the effect of these agents was greater (P < 0.01) on DBcAMP action. G protein inhibitor and pertussis toxin partially blocked the action of PTH. The data indicate that 1) PTH increases [Ca2+]i of hepatocytes; 2) this action of the hormone is receptor mediated; 3) the predominant pathway for this PTH action is the stimulation of a G protein-adenylate cyclase-cAMP system, which then leads to stimulation of a calcium transport system inhibitable by verapamil or nifedipine or activation of L-type calcium channels; 4) activation of protein kinase C is also involved; and 5) the PTH-induced rise in [Ca2+]i is due, in major parts, to movement of extracellular calcium into the cell.
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PMID:Mechanisms of PTH-induced rise in cytosolic calcium in adult rat hepatocytes. 797 36


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