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)

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

In non-differentiated NG108-15 cells, both angiotensin II (Ang II) (100 nM) and CGP 42112 (100 nM) decreased the T-type calcium current amplitude by 24 +/- 2% and 21 +/- 3%, respectively. cGMP is not a mediator of the Ang II effect, since loading of cells with 50 microM cGMP did not prevent the inhibitory effects of Ang II. The effects of Ang II involves a non-identified GTPase activity since incubation with GDP beta S (3 mM) completely reversed the inhibitory effect of Ang II while GTP gamma S mimicked its effect. However, Ang II binding was not affected by GTP gamma S, and the effect of Ang II was not modified in pertussis toxin-treated cells. The inhibitory effect of Ang II on the T-type Ca2+ current involves a phosphotyrosine phosphatase activity since sodium orthovanadate prevented the effects of Ang II, although microcystin-LR, a selective Ser/Thr phosphatase 1 and 2A inhibitor, did not modify the effect of Ang II. These results provide the first evidence of a modulation of membrane conductance by Ang II through the AT2 receptor and demonstrate the involvement of a phosphotyrosine phosphatase and a G protein in the AT2 transduction mechanism in NG108-15 cells. Moreover, our data suggest that phosphotyrosine phosphatase activation is proximal to receptor occupation, since sodium orthovanadate inhibits both GTPase activity and T-type current blockage induced by Ang II or CGP 42112, while GTP gamma S inhibition of the T-type calcium current is not impaired.
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PMID:A G protein is involved in the angiotensin AT2 receptor inhibition of the T-type calcium current in non-differentiated NG108-15 cells. 782 1

Angiotensin II (ANG II) stimulates the delayed rectifier K+ current (IK) in neurons cultured from rat hypothalamus and brain stem via AT2 receptors, and this effect involves activation of a Gi protein and protein phosphatase 2A (PP2A). However, there was no evidence that the AT2 receptor involved in this response was the same as the recently cloned AT2 receptor. In the present study, intracellular injection of a 22-amino acid peptide (PEP-22) corresponding to the putative third intracellular loop of the cloned AT2 receptor elicited an increase in IK in cultured neurons that was similar to the effect produced by ANG II. Furthermore, this effect of PEP-22 was abolished by pertussis toxin (200 ng/ml, 24 h) pretreatment and also by superfusion of the PP2A inhibitor okadaic acid (10 nM), suggesting the involvement of Gi protein and PP2A, respectively. Intracellular injection of a random peptide or normal pipette solution did not affect neuronal IK. This is direct evidence to link the cloned AT2 receptor to a defined response elicited by ANG II.
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PMID:Modulation of the delayed rectifier K+ current in neurons by an angiotensin II type 2 receptor fragment. 784 Jan 57

Angiotensin II (AII) receptors are known to interact with two distinct guanine nucleotide binding proteins, Gq/11 and Gi, in rat adrenal glomerulosa cells to activate phospholipase C and to inhibit adenylate cyclase, respectively. However, in cultured bovine glomerulosa cells AII potentiates rather than inhibits the stimulatory effect of adrenocorticotropin (ACTH) on cAMP levels. This effect of AII was partially mimicked by phorbol 12-myristate 13-acetate (PMA) and was partially inhibited by staurosporine or depletion of protein kinase C but was unaffected by pertussis toxin treatment. No potentiation was detectable in disrupted cells or in membrane preparations. In intact glomerulosa cells, treatment with cyclosporin A or FK506 completely inhibited AII- or PMA-induced potentiation of cAMP production without affecting the response to ACTH. In COS-7 cells transfected with the rat AT1 receptor, AII caused 2-3-fold enhancement of the ACTH-induced cAMP response, an effect that was partially reproduced by PMA. These potentiating actions of AII and PMA were prevented by preincubation with cyclosporin A or FK506, and the latter effect was abolished by rapamycin. These results implicate the Ca2+- and calmodulin-dependent protein phosphatase, calcineurin, in AII-induced enhancement of adenylate cyclase activity in both adrenal glomerulosa and transfected COS-7 cells. The finding that AII enhances ACTH-stimulated production of cAMP by a second messenger-mediated mechanism that involves the participation of calcineurin reveals an additional mode of cross-talk between pathways activated by Ca(2+)-mobilizing and cAMP-generating receptors.
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PMID:Evidence for participation of calcineurin in potentiation of agonist-stimulated cyclic AMP formation by the calcium-mobilizing hormone, angiotensin II. 792 24

Angiotensin II (AII) reversibly modulates calcium current in isolated neonatal rat nodose ganglion cells by two different pathways. A maximum inhibitory effect of 43 +/- 6% (n = 25) of the peak calcium current at -10 mV was observed at 10 nM AII. The IC50 of the inhibitory response was 100 pM. Losartan, a specific antagonist for the AT1 type of AII receptor, abolished the AII-induced inhibition, as did preincubation with pertussis toxin (PTX). When omega-conotoxin GVIA (CTX) was added to the bath solution, AII produced no inhibition of the remaining calcium current, indicating that the AII inhibition was mediated through CTX-sensitive calcium channels. Reversible facilitation of calcium current was seen more rarely. The AII-induced facilitation was unaffected by losartan and PTX, indicating that the effect is mediated by a non-AT1 receptor and does not depend upon a PTX-sensitive G-protein. The facilitation is present when the CTX-sensitive current has been blocked and involves activation of a reserve pool of dihydropyridine (DHP)-sensitive channels. In general, a particular neuron exhibited either inhibition or facilitation. However, in some neurons both inhibition and facilitation could be demonstrated in the presence of the appropriate blocking agents.
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PMID:Dual effects of angiotensin II on calcium currents in neonatal rat nodose neurons. 796 6

Angiotensin II (ANG II) elicits an ANG II type 2 (AT2) receptor-mediated increase in outward K+ current (IK; delayed rectifier K+ current) in neurons cocultured from rat hypothalamus and brain stem. Here we have shown that the AT2-receptor-mediated stimulation of neuronal IK by ANG II (100 nM) was abolished by pretreatment of cultures with pertussis toxin (PTX; 200 ng/ml) and by intracellular application of an antibody against the inhibitory guanine nucleotide (GTP) binding protein (anti-Gi alpha, 1:200). Antibodies against other GTP binding proteins (anti-Go alpha, 1:50 and 1:200; anti-Gq/11 alpha, 1:200) did not alter the AT2-receptor-mediated stimulation of neuronal IK by ANG II (100 nM). Furthermore, this effect of ANG II (100 nM) was inhibited by the serine/threonine phosphatase inhibitor okadaic acid (1-10 nM) and by anti-type 2A protein phosphatase (PP2A) antibodies but not by the tyrosine phosphatase inhibitor sodium orthovanadate (1 mM). Thus we have identified key components (Gi and PP2A) of the signal transduction pathway that is responsible for the AT2-receptor-mediated stimulation of neuronal K+ currents.
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PMID:Angiotensin II type 2 receptor stimulation of neuronal K+ currents involves an inhibitory GTP binding protein. 797

The unmasking of the low concentration effect of angiotensin II (AII) was identified within the concentration ranges of 10(-13) to 10(-11) M of AII by PD 121981 (5-diphenylacetyl-1-(4-methoxy-3-methylbenzyl)- 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]-pyridine-6-carboxylic acid) and 10(-12) to 3 x 10(-10) M of AII by CGP 42112 (nicotinic acid-Tyr-(N alpha-benzyl-oxycarbonyl-Arg)Lys-His-Pro-IIe-OH), AT2 antagonists, in association with the ordinary contraction curve, i.e., high concentration effect (at 3 x 10(-10)-10(-6) M of AII), in the rabbit abdominal aorta. Thus, they showed clear biphasic features of AII-induced contraction curves. However, this was not the case for angiotensin I and angiotensin III. This PD 121981-evoked low concentration effect of AII was selectively inhibited by DuP 753 (0.01-1 nM), dithiothreitol (10 and 100 microM), pertussis toxin (50 and 300 ng/ml, for 2 hr), nifedipine (1 and 10 microM) and 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (1 and 3 microM), which suggests the receptors were the AT1 subtype. However, the high concentration effect of AII was not affected by these drugs within the concentration ranges used in the present studies. These myographic results were almost consistent with the features of the intracellular Ca++ changes. Thus, it was concluded that the receptors that mediate the low concentration effect of AII belong to the AT1 subtype. However, the current study did not determine the mechanism by which PD 121981 and CGP 42112 evoked the up-regulation of the AT1 receptors.
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PMID:Characterization of PD 121981- and CGP 42112-induced unmasking of low concentration effects of angiotensin II in rabbit abdominal aorta. 799 73

In the present work we have investigated the effects of several growth factors on the expression of Angiotensin II (A-II) receptors subtype AT1 and their pertussis toxin-insensitive coupling to G-proteins in bovine adrenal fasciculata-reticularis cells (BAC). Insulin, Insulin-like growth factor and basic Fibroblast growth factor increased AT1 receptors (mRNA and binding sites) as well as the alpha subunit of Gq (mRNA and protein) and G11 (protein). These changes were associated with an enhanced A-II-induced inositol phosphate accumulation and cortisol production. In contrast, Transforming growth factor beta 1, which reduced slightly AT1 binding sites, but not the level of alpha q or alpha 11 proteins, did not change the A-II-induced inositol phosphate accumulation. However, this factor, as previously reported, markedly reduced cortisol production.
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PMID:Regulation by growth factors of angiotensin II type-1 receptor and the alpha subunit of Gq and G11 in bovine adrenal cells. 801 89

Angiotensin II has been reported to stimulate the proximal tubule Na-H antiporter by inhibition of adenylyl cyclase, and possibly by an adenosine 3',5'-cyclic monophosphate (cAMP)-independent mechanism. We examined the effect of angiotensin II on Na-H antiporter activity (JNa-H) in opossum kidney (OKP) cells, a proximal tubule-like cell line, whose Na-H antiporter resembles that of the proximal tubule apical membrane. We found that angiotensin II regulates JNa-H in a concentration-dependent manner similar to the proximal tubule, with angiotensin II concentrations < 10(-8) M stimulating and > 10(-8) M inhibiting JNa-H. The stimulatory effect of angiotensin II was blocked by 10(-8) M losartan and was pertussis toxin sensitive, suggesting mediation through an angiotensin II (AT1) receptor coupled to a pertussis toxin-sensitive G protein. Acute treatment with 10(-4) M 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) inhibited JNa-H by 30% and blocked angiotensin II-induced stimulation. However, angiotensin II (10(-12)-10(-6) M) did not inhibit basal, dopamine-stimulated, or forskolin-stimulated cAMP production measured in the presence of 3-isobutyl-1-methylxanthine (IBMX). In addition, angiotensin II had no effect on cAMP levels measured in the absence of IBMX. We conclude that angiotensin II at physiological concentrations stimulates JNa-H in OKP cells via a cAMP-independent mechanism mediated by an AT1 receptor and a pertussis toxin-sensitive G protein.
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PMID:Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells. 802 91


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