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 present study examined the effect of dopamine on rat jejunal electrolyte transport (rheogenic transport and Na+, K(+)-ATPase activity) in adult (60-day old) and young (20-day old) animals. 2. In young rats, dopamine, in the presence of phentolamine, produced an increase in jejunal Isc, this being completely abolished by SKF 83566, and not changed by S-sulpiride. SKF 38393, but not quinerolane, also increased Isc; this effect was abolished by SKF 83566 and ouabain, but not by furosemide. In adult rats, dopamine in the presence of phentolamine (0.2 microM) decreased Isc. 3. Na+, K(+)-ATPase activity in isolated jejunal epithelial cells from adult rats was 2.4 fold that in young rats. In the presence of phentolamine, both dopamine and SKF 38393, but not quinerolane, significantly decreased jejunal Na+, K(+)-ATPase activity in young animals but not in adult animals. 4. Binding [3H]-Sch 23390 to membranes of jejunal mucosa revealed the presence of a single class of receptors in both young and adult rats, with similar KD and Bmax values. 5. GTP gamma S and cholera toxin inhibited jejunal Na+, K(+)-ATPase activity in young, but not in adult rats. Co-incubation of pertussis toxin with dopamine was found to potentiate the inhibitory effects of dopamine upon the enzyme in both young and adult rats. 6. Regulation of Na+, K(+)-ATPase activity by cholera toxin-sensitive G proteins is absent in adult animals, and such difference may explain the failure of dopamine to inhibit intestinal Na+, K(+)-ATPase activity in adult rats.
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PMID:Ontogenic aspects of D1 receptor coupling to G proteins and regulation of rat jejunal Na+, K+ ATPase activity and electrolyte transport. 1071 57

UTP stimulates transmitter release and inhibits M-type K(+) channels in rat superior cervical ganglion neurons via G protein-coupled P2Y receptors. To investigate the underlying signaling mechanisms, we treated the neurons with either pertussis or cholera toxin; neither treatment altered the inhibition of M-type K(+) channels by 10 microM UTP. However, pertussis toxin reduced UTP-evoked [(3)H]noradrenaline release by 66%. UTP, UDP, ATP, and ADP caused accumulation of inositol trisphosphate in a pertussis toxin-insensitive manner. Pharmacological inhibition of inositol trisphosphate-induced Ca(2+) release (by inhibition of phospholipase C, of inositol trisphosphate receptors, and of the endoplasmic Ca(2+)-ATPase) prevented the UTP-dependent inhibition of M currents but failed to alter UTP-evoked [(3)H]noradrenaline release. Chelation of intracellular Ca(2+) by 1,2-bis(2-aminophenoxy)ethane-N, N,N',N'-tetraacetic acid also reduced the inhibition of M currents by UTP. In addition, all these manipulations attenuated the inhibition of M currents by bradykinin, but hardly affected the inhibitory action of oxotremorine M. These results demonstrate that UTP inhibits M-type K(+) channels via an inositol trisphosphate-dependent signaling cascade that is also used by bradykinin but not by muscarinic acetylcholine receptors. In contrast, the secretagogue action of UTP is largely independent of this signaling cascade but involves pertussis toxin-sensitive G proteins. Thus, UTP-sensitive P2Y receptors excite sympathetic neurons via at least two different signal transduction mechanisms.
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PMID:Two different signaling mechanisms involved in the excitation of rat sympathetic neurons by uridine nucleotides. 1082 87

The cellular distribution of Ca(2+)-inhibitable adenylyl cyclase (AC) type 5 and type 6 mRNAs in rat outer medullary collecting duct (OMCD) was performed by in situ hybridization. Kidney sections were also stained with specific antibodies against either collecting duct intercalated cells or principal cells. The localization of type 5 AC in H(+)-ATPase-, but not aquaporin-3-, positive cells demonstrated that type 5 AC mRNA is expressed only in intercalated cells. In contrast, type 6 AC mRNA was observed in both intercalated and principal cells. In microdissected OMCDs, the simultaneous superfusion of carbachol and PGE(2) elicited an additive increase in the intracellular Ca(2+) concentration, suggesting that the Ca(2+)-dependent regulation of these agents occurs in different cell types. Glucagon-dependent cAMP synthesis was inhibited by both a pertussis toxin-sensitive PGE(2) pathway (63.7 +/- 4.6% inhibition, n = 5) and a Ca(2+)-dependent carbachol pathway (48.6 +/- 3.3%, n = 5). The simultaneous addition of both agents induced a cumulative inhibition of glucagon-dependent cAMP synthesis (78.2 +/- 3.3%, n = 5). The results demonstrate a distinct cellular localization of type 5 and type 6 AC mRNAs in OMCD and the functional expression of these Ca(2+)-inhibitable enzymes in intercalated cells.
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PMID:Cellular localization of type 5 and type 6 ACs in collecting duct and regulation of cAMP synthesis. 1089 1

Bordetella pertussis is readily killed after uptake by professional phagocytes, whereas its close relative Bordetella bronchiseptica is not and can persist intracellularly for days. Phagocytosis of members of either species by a mouse macrophage cell line results in transport of the bacteria to a phagosomal compartment positive for the lysosome-associated membrane protein 1, the protease cathepsin D, and the late endosomal vacuolar proton-pumping ATPase but negative for the early endosome antigen 1 and the early endosomal transferrin receptor. In addition, we demonstrate that Bordetella-containing phagosomes rapidly acidify to pH 4.5 to 5.0. Taken together, these data demonstrate that Bordetella-containing phagosomes rapidly mature to an acidic late endosomal/lysosomal compartment. Following up on this observation, we determined that B. pertussis does not survive in bacterial growth media adjusted to a pH of 4.5, whereas this pH has only minor effects on the growth of B. bronchiseptica. Raising the intracellular pH in infected macrophages by the addition of bafilomycin A(1), ammonium chloride, or monensin increases the survival of acid-sensitive B. pertussis but, surprisingly, decreases that of acid-tolerant B. bronchiseptica. In summary, we hypothesize that the differential survival of B. pertussis and B. bronchiseptica in macrophages is, at least in part, due to the differences in their acid tolerance.
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PMID:Phagosome acidification has opposite effects on intracellular survival of Bordetella pertussis and B. bronchiseptica. 1108 29

We have earlier shown that the renal dopaminergic system failed to respond to high salt (HS) intake in old (24-month-old) Fisher 344 rats (Hypertension 1999;34:666-672). In the present study, intestinal Na+,K+-ATPase activity and intestinal dopaminergic tonus were evaluated in adult and old Fischer 344 rats during normal salt (NS) and HS intake. Basal intestinal Na+,K+-ATPase activity (nmol Pi/mg protein/min) in adult rats (142+/-6) was higher than in old Fischer 344 rats (105+/-7). HS intake reduced intestinal Na+,K+-ATPase activity by 20% (P<0.05) in adult, but not in old rats. Dopamine (1 microM) failed to inhibit intestinal Na+,K+-ATPase activity in both adult and old Fischer 344 rats (NS and HS diets). In adult animals, co-incubation of pertussis toxin with dopamine (1 microM) produced a significant inhibitory effect in the intestinal Na+,K+-ATPase activity. L-DOPA and dopamine tissue levels in the intestinal mucosa of adult rats were higher (45+/-9 and 38+/-4 pmol/g) than those in old rats (27+/-9 and 14+/-1 pmol/g). HS diet did not change L-DOPA and DA levels in both adult and old rats. DA/L-DOPA tissue ratios, an indirect measure of dopamine synthesis, were higher in old (1.1+/-0.2) than in adult rats (0.6+/-0.1). Aromatic L-amino acid decarboxylase (AADC) activity in the intestinal mucosa of old rats was higher than in adult rats. HS diet increased the AADC activity in adult rats, but not in old rats. It is concluded that intestinal dopaminergic tonus in old Fisher 344 rats is higher than in adult rats and is accompanied by lower basal intestinal Na+,K+-ATPase activity. In old rats, HS diet failed to alter the intestinal dopaminergic tonus or Na+,K+-ATPase activity, whereas in adult rats increases in AADC activity were accompanied by decreases in Na+,K+-ATPase activity. The association between salt intake, increased dopamine formation and inhibition of Na+,K+-ATPase at the intestinal level was not as straightforward as that described in renal tissues.
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PMID:Salt intake and intestinal dopaminergic activity in adult and old Fischer 344 rats. 1158 11

1. Using a Ca(2+) imaging system and fura-2 AM (5 microM) we showed that exposure of polarised monolayers of human bronchial epithelial cells (16HBE14o- cell line) to aldosterone produced a fast intracellular [Ca(2+)] ([Ca(2+)](i)) decrease, in 70 % of cells. Exposure to aldosterone (1 nM) reduced the [Ca(2+)](i) by 39 +/- 9 nM (n = 282, P < 0.0001) within 10 min, from a basal [Ca(2+)](i) of 131 +/- 19 nM (n = 282). 2. The effect of aldosterone on [Ca(2+)](i) was not affected by inhibitors of the classical genomic pathway, cycloheximide (1 microM) or spironolactone (10 microM). The aldosterone-induced [Ca(2+)](i) decrease was inhibited by thapsigargin (1 microM), pertussis toxin (24 h at 200 ng ml(-1)), the adenylate cyclase inhibitors 2',3'-dideoxyadenosine (200 microM) and MDL-12,330A hydrochloride (500 microM), and the protein kinase A inhibitor R(P)-adenosine 3',5'-cyclic monophosphorothioate (200 microM). In addition, treatment of 16HBE14o- monolayers with aldosterone (1 nM) inhibited by approximately 30 % the large and transient [Ca(2+)](i) increase induced by apical exposure to uridine triphosphate (UTP, 0.1 mM), a known secretagogue in airway epithelia. 3. Our results demonstrate for the first time that in human bronchial epithelial cells, aldosterone decreases [Ca(2+)](i) levels via a non-genomic mechanism. The hormone-induced changes to [Ca(2+)](i) involve stimulation of thapsigargin-sensitive Ca(2+)-ATPase, via G-protein-, adenylate cyclase- and protein kinase A-coupled signalling pathways.
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PMID:Rapid and non-genomic reduction of intracellular [Ca(2+)] induced by aldosterone in human bronchial epithelium. 1171 79

Parathyroid hormone (PTH) and dopamine (DA) inhibit Na-K ATPase activity and sodium-phosphate cotransport in proximal tubular cells. We previously showed that PTH and DA inhibit phosphate transport in opossum kidney (OK) cells through different signaling pathways. Therefore, we hypothesized that PTH and DA also inhibit Na-K ATPase through divergent pathways. We measured PTH and DA inhibition of Na-K ATPase activity in the presence of inhibitors of signaling pathways. PTH and DA inhibited Na-K ATPase in a biphasic manner, the early inhibition through protein kinase C (PKC)- and phospholipase A(2) (PLA(2))-dependent pathways and the late inhibition through protein kinase A- and PLA(2)-dependent pathways. Inhibition of extracellular signal-regulated kinase (ERK) activation blocked early and late inhibition of Na-K ATPase by PTH but not by DA. Pertussis toxin blocked early and late inhibition by DA but not by PTH. Treatment with DA, but not PTH, resulted in an early downregulation of basolateral membrane expression of the alpha-subunit, whereas total cellular expression remained constant for both agonists. We conclude that PTH and DA regulate Na-K ATPase by different mechanisms through activation of divergent pathways.
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PMID:PTH and DA regulate Na-K ATPase through divergent pathways. 1183 34

Somatostatin, a hormone that signals via G(i)/G(o), usually inhibits increases in intracellular calcium concentration ([Ca(2+)](i)) and insulin release from beta-cells. We have found that in the presence of arginine vasopressin (AVP), which signals via G(q), somatostatin increased [Ca(2+)](i), leading to insulin release in HIT-T15 cells. The increase in [Ca(2+)](i) by somatostatin was observed even after 60 min of AVP treatment. Somatostatin alone failed to increase [Ca(2+)](i) and insulin release. Somatostatin induced changes in [Ca(2+)](i) in a biphasic pattern, characterized by a sharp and transient increase followed by a rapid decline to sub-basal levels. Pretreatment with pertussis toxin, which inactivates G(i)/G(o), abolished the effects of somatostatin. U-73122, an inhibitor of phospholipase C, antagonized the somatostatin-induced increase in [Ca(2+)](i). In Ca(2+)-free medium, somatostatin still increased [Ca(2+)](i). Depletion of intracellular Ca(2+) stores with thapsigargin, a microsomal Ca(2+)-ATPase inhibitor, abolished somatostatin's effect. In the presence of bradykinin, another G(q)-coupled receptor agonist, somatostatin also increased [Ca(2+)](i), but not in the presence of isoproterenol (a G(s)-coupled receptor agonist) or medetomidine (a G(i)/G(o)-coupled receptor agonist). Our findings suggest that somatostatin signals through G(i)/G(o), and involves phospholipase C and Ca(2+) release from the endoplasmic reticulum. The increase in [Ca(2+)](i) by somatostatin leads to insulin release. This cross-talk is specific to G(q) and G(i)/G(o), and is not limited to the AVP and somatostatin receptors.
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PMID:Somatostatin-induced paradoxical increase in intracellular Ca2+ concentration and insulin release in the presence of arginine vasopressin in clonal HIT-T15 beta-cells. 1198 73

This study examined the effects of D2-like dopamine receptor activation on Na+-K+-ATPase activity while apical-to-basal, ouabain-sensitive, amphotericin B-induced increases in short-circuit current and basolateral K+ (I(K)) currents in opossum kidney cells were measured. The inhibitory effect of dopamin on Na+-K+-ATPase activity was completely abolished by either D1- or D2-like receptor antagonists and mimicked by D1- and D2-like receptor agonists SKF-38393 and quinerolane, respectively. Blockade of basolateral K+ channels with BaCl2 (1 mM) or glibenclamide (10 microM), but not apamin (1 microM), totally prevented the inhibitory effects of quinerolane. The K+ channel opener pinacidil decreased Na+-K+-ATPase activity. The inhibitory effect of quinerolane on Na+-K+- ATPase activity was abolished by pretreatment of opossum kidney cells with pertussis toxin (PTX). Quinerolane increased I(K) across the basolateral membrane in a concentration-dependent manner; this effect was abolished by pretreatment with PTX, S-sulpiride, and glibenclamide. SKF-38393 did not change I(K). Both H-89 (protein kinase A inhibitor) and chelerythrine (protein kinase C inhibitor) failed to prevent the stimulatory effect of quinerolane on I(K). The stimulation of the D2-like receptor was associated with a rapid hyperpolarizing effect, whereas D1-like receptor activation was accompanied by increases in cell membrane potential. It is concluded that stimulation of D2-like receptors leads to inhibition of Na+-K+-ATPase activity and hyperpolarization; both effects are associated with the opening of K+ channels.
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PMID:D2-like receptor-mediated inhibition of Na+-K+-ATPase activity is dependent on the opening of K+ channels. 1206 May 93

The proinsulin C-peptide has been held to be merely a by-product in insulin biosynthesis, but recent reports show that it elicits both molecular and physiological effects, suggesting that it is a hormonally active peptide. Specific binding of C-peptide to the plasma membranes of intact cells and to detergent-solubilised cells has been shown, indicating the existence of a cell surface receptor for C-peptide. C-peptide elicits a number of cellular responses, including Ca(2+) influx, activation of mitogen-activated protein (MAP) kinases, of Na(+),K(+)-ATPase, and of endothelial NO synthase. The pentapeptide EGSLQ, corresponding to the C-terminal five residues of human C-peptide, mimics several of the effects of the full-length peptide. The pentapeptide displaces cell membrane-bound C-peptide, elicits transient increase in intracellular Ca(2+) concentration and stimulates MAP kinase signalling pathways and Na(+),K(+)-ATPase. The Glu residue of the pentapeptide is essential for displacement of the full-length C-peptide, and free Glu can partly displace bound C-peptide, suggesting that charge interactions are important for receptor binding. Many C-peptide effects, such as phosphorylation of MAP-kinases ERK 1 and 2, stimulation of Na(+),K(+)-ATPase and increases in intracellular calcium concentrations are inhibited by pertussis toxin, supporting interaction of C-peptide with a G-protein-coupled receptor. However, all C-peptide effects cannot be explained in this manner, and it is possible that additional interactions are involved. Combined, the available observations show that C-peptide is biologically active and suggest a molecular model for its physiological effects.
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PMID:Molecular effects of proinsulin C-peptide. 1213 97


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