Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The short term regulation of the activity of the Na,K-pump (Na+,K(+)-ATPase) is just beginning to be understood. By using single microdissected proximal tubule segments (PCT) (permeabilized in order to clamp Na entry), it was possible to study regulation of Na+,K(+)-ATPase activity in its own environment and in a well defined cell population. The Na+,K(+)-ATPase activity can be regulated over a short term via guanidine triphosphate (GTP) dependent regulatory proteins. However the guanidine proteins are not directly coupled to the Na,K-pump and the mechanism involves the activation of complex intracellular signalling system. Locally produced dopamine induces a dose dependent inhibition of Na+,K+ ATPase activity. This inhibition is mediated by a complex mechanism that requires the activation of both membrane dopamine receptors, DA-1 and DA-2. It involves the activation of a pertussis toxin sensitive GTP-binding protein and activation of protein kinase C. A DA-2 agonist only inhibits Na+,K(+)-ATPase activity when it is incubated together with dibutyryl cAMP or Forskolin. We have therefore concluded that an increase in cellular cAMP levels plays a permissive role for DA-2 inhibition of Na+,K(+)-ATPase activity. A fully differentiated cell is required for dopamine inhibition of Na+,K(+)-ATPase activity. An abnormal regulation of proximal tubule Na+,K(+)-ATPase activity might be of importance in the pathogenesis of certain types of hypertension.
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PMID:Short-term regulation of Na+,K(+)-ATPase activity by dopamine. 216 34

A study was conducted to investigate nephritogenic tubular basement membrane antigens common to human and rat kidneys. Brown Norway (BN) rats were immunized with human renal basement membrane in complete Freund's adjuvant simultaneously with Bordetella pertussis vaccine. The immunized rats developed polyuria and increased levels of serum creatinine one week after the second immunization. Renal histology at this time revealed marked, acute tubulointerstitial nephritis with linear deposition of IgG and C3 along the tubular basement membrane and Bowman's capsule, but not along the glomerular basement membrane. Rats with this tubulointerstitial nephritis rapidly developed antibodies against renal antigens from normal BN rats such as tubular basement membrane and proximal tubule brush border, however antibodies to glomerular basement membrane appeared later. Western blotting using the same rat sera detected a 145-kDa antigen from 8 M urea-solubilized human renal basement membrane and 120-kDa, 135-kDa and 145-kDa antigens from 8 M urea-solubilized BN rat renal basement membrane. This suggests that renal basement membranes of human and rat origin have common antigens involved in the pathogenesis of tubulointerstitial nephritis.
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PMID:Induction of interstitial nephritis in rats by basement membrane of human origin. 268 56

Parathyroid hormone enhances the formation of cAMP and decreases the Na+-dependent uptake of phosphate in cultured renal cells derived from the American opossum (OK cells). Epinephrine, acting as an alpha 2-adrenergic agonist, inhibits the PTH-induced synthesis of cAMP by a pertussis toxin-sensitive mechanism and blunts the inhibition of phosphate transport by PTH. Na+-dependent alpha-methylglucoside and Na+ uptakes by the cells are unaffected by PTH and epinephrine. These findings suggest that alpha 2-adrenergic agonists may selectively modulate PTH-sensitive phosphate transport in the renal proximal tubule.
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PMID:Alpha-2-adrenergic modulation of the parathyroid hormone-inhibition of phosphate uptake in cultured renal (OK) cells. 284 89

Studies of permeabilized rat renal proximal convoluted tubules have demonstrated that NaKATPase activity can be inhibited by locally produced DA. The effect is mediated by a pertussis toxin sensitive inhibitory G-protein. DA inhibition of proximal tubule NaKATPase activity is of physiological importance. During high salt diet renal DA production is increased and the inhibitory effect of DA on NaKATPase is enhanced. DA inhibition of NaKATPase activity will contribute to the natriuresis during high salt diet.
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PMID:Dopamine inhibition of NaKATPase activity in proximal convoluted tubule cells. 284 29

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

Receptor-mediated endocytosis and recycling have been described for extrarenal angiotensin II (ANG II) receptors. In proximal tubule (PT) epithelia expressing polarized ANG II receptors, these processes have not been examined as thoroughly. We utilized a PT cell model, LLC-PKCl4 cells stably transfected with rabbit type 1 ANG II receptor (AT1R) cDNA, to investigate these properties. LLC-PK-AT1R cells expressed the rabbit AT1R transcript and displayed losartan-inhibitable specific 125I-labeled ANG II binding at apical (AP) and basolateral (BL) membranes when grown on permeable supports. AP AT1R internalized 125I-ANG II more rapidly than BL AT1R, and phenylarsine oxide treatment inhibited AP AT1R internalization without significantly affecting BL AT1R endocytosis. Pertussis toxin had no effect on AP or BL AT1R endocytosis. In addition, AP AT1R recovered specific 125I-ANG II binding after ANG II treatment (a measure of recycling). BL AT1R displayed minimal recovery of 125I-ANG II binding after ANG II pretreatment. These data suggested that AP AT1R enter endocytic/endosomal pathways. Phospholipase A2 (PLA2) activity has been linked to endosomal fusion in other systems, and PT brush-border membrane AT1R also have been associated with PLA2 activity. LLC-PK-AT1R cells were therefore treated with quinacrine, a nonspecific PLA2 inhibitor, or Compound I (CI), a selective Ca(2+)-independent PLA2 inhibitor, to determine if PLA2 activity was linked to AT1R recycling. Both quinacrine and CI decreased AP AT1R recycling without affecting BL AT1R recycling. Polarized AT1R in LLC-PKCl4 cells thus display differential rates of endocytosis and recycling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polarized rabbit type 1 angiotensin II receptors manifest differential rates of endocytosis and recycling. 748 45

Purinergic P2 receptors are present on proximal renal tubules, but their function is unknown. Because P2 agonists antagonize vasopressin-stimulated water transport in the distal tubule by inhibiting activation of adenylyl cyclase, we postulated that P2 receptor activation blocks parathyroid hormone (PTH) inhibition of phosphate uptake in proximal tubule by preventing PTH-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation. PTH inhibition of sodium-dependent phosphate uptake was attenuated by alpha,beta-methylene-ATP (AMP-CPP), a P2x receptor agonist, but not by 2-methyl-thio-ATP, a P2y receptor agonist, in a dose-dependent manner. AMP-CPP did not attenuate inhibition of phosphate uptake produced by direct activation of adenylyl cyclase with forskolin, by addition of the cAMP analogue 8-bromo-cAMP, or by inhibition of cAMP phosphodiesterase with RO-20-1724. Additionally, AMP-CPP had no effect on basal or PTH-stimulated cAMP production. As PTH also stimulates protein kinase C activation, the effect of AMP-CPP on inhibition of phosphate uptake stimulated by phorbol 12-myristate 13-acetate (PMA) was tested. AMP-CPP had no effect on PMA-induced inhibition of phosphate uptake. Pretreatment with pertussis toxin abolished the attenuating effect of AMP-CPP on PTH inhibition of sodium-dependent phosphate uptake. We conclude that activation of purinergic P2 receptors attenuates the inhibitory effect of PTH on sodium-dependent phosphate uptake by a G protein-dependent mechanism that is independent of cAMP generation protein kinase A activation, or protein kinase C activation.
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PMID:P2 purinoceptor stimulation attenuates PTH inhibition of phosphate uptake by a G protein-dependent mechanism. 757 78

Angiotensin II (ANG II) receptors of the AT1 subtype are present on the apical and basolateral membranes of renal proximal tubule cells. Cells of the proximal tubulelike cell line, LLC-PK1/Cl4, were transfected with an expression plasmid containing cDNA encoding the rabbit AT1 ANG II receptor. In transfected cells, specific binding of 125I-ANG II was detected on both apical and basolateral membranes; wild-type LLC-PK1/Cl4 cells did not express ANG II receptors. In transfected cells, apical or basolateral ANG II increased both S6 kinase activity and incorporation of [3H]leucine. In cells pretreated with pertussis toxin, the stimulatory effect of apical or basolateral ANG II on [3H]leucine incorporation was abolished. In contrast, ANG II did not affect mitogenesis, determined by [3H]thymidine incorporation. Apical or basolateral ANG II (10(-6) M) stimulated phosphoinositide turnover by 13.4 +/- 4.4% (n = 8) and 16.3 +/- 4.2% (n = 9), respectively. The activity of protein kinase C, determined by phosphorylation of a specific protein kinase C peptide substrate, was also stimulated by ANG II in transfected cells. Apical or basolateral ANG II had no significant effect on cellular adenosine 3',5'-cyclic monophosphate levels. In permeabilized transfected cells, apical ANG II (10(-6) M) inhibited the phosphorylation of a specific peptide substrate of protein kinase A; lower apical concentrations or basolateral ANG II were without significant effect. These results indicate that AT1 ANG II receptors sort to both apical and basolateral membranes in renal epithelial cells and are coupled to activation of phospholipase C. ANG II stimulates protein synthesis by binding to either apical or basolateral receptors; this effect requires coupling to G proteins and may be mediated by activation of S6 kinase. Because high concentrations of ANG II exist in proximal tubule, binding to apical and basolateral receptors may regulate proximal tubule cell growth under physiological conditions.
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PMID:Signaling and growth responses of LLC-PK1/Cl4 cells transfected with the rabbit AT1 ANG II receptor. 773 40

Angiotensin II (Ang II) is an important regulator of proximal tubule salt and water reabsorption. Recent studies indicate that rabbit proximal tubule angiotensin II receptors are the type-1 (AT1R) subtype. We studied the effect of Ang II on proximal tubule receptor expression. Rabbits were treated with either angiotensin converting enzyme inhibitors or a low salt diet to modulate endogenous Ang II levels. In captopril-treated rabbits, liver and glomerular AT1R mRNA levels increased 242 +/- 125 and 141 +/- 60%, respectively (n = 6-7; P < 0.05), as determined by quantitative PCR. In contrast, proximal tubule AT1R mRNA levels decreased 40 +/- 11% (n = 6; P < 0.05). Binding of 125I Ang II to renal cortical basolateral membranes of captopril-treated rabbits decreased from 2.9 +/- 0.55 to 1.4 +/- 0.17 fmol/mg protein (n = 6; P < 0.025). In rabbits fed a sodium chloride-deficient diet for 4 wk, AT1R mRNA levels decreased 52 +/- 11% in liver and 43 +/- 7% in glomeruli (n = 4-5; P < 0.05), whereas they increased 141 +/- 85% (n = 5; P < 0.05) in proximal tubule. In basolateral membranes from rabbits on the sodium chloride-deficient diet, specific binding of 125I Ang II increased from 2.1 +/- 0.2 to 4.3 +/- 1.1 fmol/mg protein (n = 7; P < 0.05). To determine whether Ang II directly regulates expression of proximal tubule AT1 receptors, further studies were performed in cultured proximal tubule cells grown from microdissected S1 segments of rabbit proximal tubules and immortalized by transfection with a replication-defective SV40 vector. Incubation of these cells with Ang II (10(-11) to 10(-7) M) led to concentration-dependent increases in both AT1R mRNA levels and specific 125I Ang II binding. Pretreatment with pertussis toxin inhibited Ang II stimulation of AT1R mRNA. AT1R mRNA expression was decreased by either forskolin or a nonhydrolyzable cAMP analogue (dibutryl cAMP). Simultaneous Ang II administration overcame the inhibitory effect of forskolin but not dibutryl cAMP. These results indicate that proximal tubule AT1R expression is regulated by ambient Ang II levels, and Ang II increases AT1R mRNA at least in part by decreasing proximal tubule cAMP generation through a pertussis toxin-sensitive mechanism. Upregulation of proximal tubule AT1R by Ang II may be important in mediating enhanced proximal tubule sodium reabsorption in states of elevated systemic or intrarenal Ang II.
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PMID:Angiotensin II upregulates type-1 angiotensin II receptors in renal proximal tubule. 773 68

Enhanced salt reabsorption by the kidney, which may arise from impaired regulation of proximal tubule Na(+)-K(+)-ATPase activity, has a central role in the pathogenesis of essential hypertension. Guanine nucleotide binding proteins (G proteins) are involved in many regulatory pathways and have been implicated in the regulation of proximal tubule Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. The present study was designed to evaluate further the regulation of Na(+)-K(+)-ATPase activity by G proteins in proximal tubule suspensions from Wistar-Kyoto rats (WKY) and to determine whether such regulation is abnormal in spontaneously hypertensive rats (SHR). Cholera toxin (CTX) inhibited Na(+)-K(+)-ATPase activity by approximately 40% in WKY but had no effect on Na(+)-K(+)-ATPase activity in SHR. In WKY, pretreatment of tubules with pertussis toxin (PTX), followed by the application of dopamine, inhibited Na(+)-K(+)-ATPase activity significantly, compared with the inhibition produced by dopamine alone. In SHR, dopamine alone did not inhibit Na(+)-K(+)-ATPase activity. However, in the presence of PTX, dopamine inhibited Na(+)-K(+)-ATPase activity significantly. These studies indicate that the renal proximal tubule Na(+)-K(+)-ATPase in WKY is regulated by both a PTX- and CTX-sensitive G protein(s) and that this regulation is abnormal in SHR. Such a defect could cause enhanced sodium reabsorption in SHR and contribute to the pathogenesis of hypertension in this model.
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PMID:Abnormal regulation of renal proximal tubule Na(+)-K(+)-ATPase by G proteins in spontaneously hypertensive rats. 781 Jun 94


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