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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (ANG II) was shown to modulate transport in the renal proximal tubule through both inhibition of adenylate cyclase and protein kinase C (PKC) activation. We evaluated the effects of ANG II on adenosine 3',5'-cyclic monophosphate (cAMP) content and Na-H exchange activity (amiloride-sensitive Na influx) in two strains of opossum kidney (OK) cells originating from different sources, OK-VD and OK-RR cells. In OK-VD cells, ANG II inhibited basal and parathyroid hormone (PTH)-induced cAMP generation in a pertussis toxin-sensitive manner and reversed PTH inhibition of Na-H exchange. These effects of ANG II were prevented by PD 123319, a selective nonpeptide antagonist of AT2 receptors. In contrast, DuP 753, which antagonizes selectively AT1 receptors, had no effect. In OK-RR cells, ANG II had no effect on cAMP content and decreased Na-H exchange activity. The effect of ANG II persisted in the presence of PTH but was abolished by PKC downregulation and by DuP 753, but not by PD 123319. In conclusion, two types of ANG II receptors, coupled to distinct signaling pathways, were expressed independently in OK cells originating from two different sources and mediated opposite effects of ANG II on Na-H exchange activity. Those models provide a powerful tool for studying the intracellular steps involved in the tubular effects of ANG II and to evaluate the effect of pharmacological inhibitors of ANG II binding to its receptors.
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PMID:Modulation of Na-H exchange activity by angiotensin II in opossum kidney cells. 133 86

The selective angiotensin (ANG II) antagonists losartan (DuP 753) and PD 123319 have been shown to bind selectively to AT1 and AT2 subtypes, respectively. To characterize ANG II receptor subtypes in mesangial cells, washed membranes were incubated with 0.1 to 0.5 nM 125I-ANG II and increasing concentrations of competitors. The inhibition of 125I-ANG II binding by losartan and PD 123319 was biphasic, and LIGAND curve-fitting analysis revealed two populations of specific binding sites. One subpopulation comprised 86% of the total and showed high affinity for ANG II and losartan, but low affinity for the AT2 antagonists PD 123319 and CGP42112A, and thus appear identical to the recently cloned AT1 subtype. The remaining 14% of the sites showed nearly 100-fold lower affinity for losartan and 10,000-fold higher affinity for PD 123319 relative to AT1 sites. However, another AT2-selective antagonist, CGP42112A, showed little affinity for these sites. Both classes of binding sites were inhibited by guanosine 5'-O-(3-thiophosphate) and pertussis toxin treatment. We propose that there are two distinct G protein-coupled ANG II receptor subtypes (AT1A and AT1B) present in renal mesangial cells.
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PMID:Angiotensin II receptor subtypes in cultured rat renal mesangial cells. 141 69

Angiotensin II (AT) receptor subtypes (AT1, selectively displaced by DuP 753, and AT2, selectively displaced by PD123177 and CGP42112A) were characterized by quantitative autoradiography after incubation with the AT agonist 125I-Sar1-AT, in specific brain nuclei of young (2-week-old) rats. Binding to AT1 receptors was sensitive (decreased affinity) to incubation in the presence of guanosine 5'-O-(3-thio)triphosphate (GTP gamma S). Only the AT1 receptors in the paraventricular nucleus were sensitive to pertussis toxin, indicating the possibility of the existence of AT1 receptor subtypes. The sensitivity of AT2 receptors to GTP gamma S was heterogeneous. In the ventral thalamic and medial geniculate nuclei and in the locus coeruleus, binding to AT2 receptors was sensitive to GTP gamma S and to pertussis toxin pretreatment. Conversely, in the inferior olive, binding was insensitive to GTP gamma S and to pertussis toxin pretreatment. We propose the nomenclature of AT2A receptors for those receptors sensitive to guanine nucleotides and pertussis toxin and that of AT2B receptors for those showing no sensitivity to guanine nucleotides or pertussis toxin treatment.
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PMID:Heterogeneity of angiotensin II AT2 receptors in the rat brain. 153 9

The mRNA level of the type-1 angiotensin II receptor (AT1) was down-regulated by angiotensin II in cultured rat glomerular mesangial cells. The effect was maximum with 1 microM AII at 6 h, sensitive to cycloheximide, and specific to AT1 since this phenomenon was blocked by DuP753, an AT1 antagonist, but not by type-2 antagonist PD123319. Dibutyryl cAMP, forskolin, and cholera toxin also caused AT1 down-regulation. These effects were not altered by either the protein kinase A inhibitor H-8 or cycloheximide. Calcium ionophore A23187, pertussis toxin, protein kinase C inhibitor staurosporine, or prolonged incubation with phorbol ester were without effect. These results suggest that there are at least two pathways to down-regulate AT1 mRNA; one way is an angiotensin II-induced, protein kinase C-independent, and cycloheximide-sensitive pathway and the other is an angiotensin II-independent, cAMP-induced, and cycloheximide-insensitive pathway.
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PMID:Two distinct pathways in the down-regulation of type-1 angiotension II receptor gene in rat glomerular mesangial cells. 159 49

In the present study, we demonstrate the presence of Ca(2+)-activated K+ channels in rat glomerulosa cells. We find that angiotensin II (Ang II) inhibits this charybdotoxin-sensitive current. The effect of Ang II was dose-dependent with an inhibition constant (Ki) of 0.98 nM and a maximal effect observed at 200 nM. Time course of the blockage was as rapid as the one induced by charybdotoxin. This effect is mediated by the AT1 receptor subtype of Ang II, since it is blocked by DUP 753 but is unaffected by CGP 42112. Activation of protein kinase C by phorbol dibutyrate (1 microM) or dialysis of the cell with inositol 1,4,5-triphosphate (20 microM) were ineffective in blocking the current. However, experiments done with GDP beta S and GTP gamma S indicated that a G protein was involved. The inhibitory effect of Ang II was not pertussis toxin-sensitive, which excludes Gi protein, but was abrogated if an antibody raised against the alpha-subunit of the Gq/11 protein was present in the patch pipette medium. Further analysis showed that the Ca(2+)-activated K+ channel was able to modulate the membrane potential according to the level of intracellular calcium concentration ([Ca2+]i). Whereas a thapsigargin-induced increase in [Ca2+]i hyperpolarized the membrane, this effect was not observed when Ang II was used to increase [Ca2+]i because of the blockage of the Ca(2+)-activated K+ current. The blockage of Ca(2+)-activated K+ current by Ang II would result in a synergistic effect on the Ang II-induced depolarization, thus favoring Ca2+ influx, an event essential to secretion.
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PMID:Modulation of a Ca(2+)-activated K+ channel by angiotensin II in rat adrenal glomerulosa cells: involvement of a G protein. 747 91

Complementary DNAs for angiotensin II type 1 receptor isoforms AT1A and AT1B were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. The AT1 type receptor interacted with more than one type of G-proteins. The ligand binding site of AT1 involving Arg167, Lys199, and Asp263 has been identified by site directed mutagenesis. The regulation of the receptors occur at many stages. The isoform, AT2, was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by stable GTP analogs, it is a seven transmembrane domain receptor. It mediates the modulations of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A. The modulation was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms. AT1 mediates cellular growth. Interestingly, AT2 expression is inversely related to the mitogenic activity of cells.
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PMID:Cloning, expression and regulation of angiotensin II receptors. 748 33

Two major isoforms of angiotensin II receptors, AT1 and AT2, have been defined on the basis of their ligand selectivity. While AT1 is known to mediate typical biological actions of angiotensin II as a cardiovascular regulator, the biological function of AT2 has not yet been established. In the present study using a rat pheochromocytoma cell line, which expresses AT2 exclusively, we found that angiotensin II inhibits phosphotyrosine phosphatase activity in vivo as measured by the inhibition of hydrolysis of [32P]-phosphate from the 32P-labeled synthetic peptide substrate, Raytide. This phosphotyrosine phosphatase inhibition was completely reversed by pertussis toxin, which indicates a G-protein coupled mechanism. In SDS-polyacrylamide gel electrophoresis we found that the phosphotyrosine group of an 85 kDa protein was a substrate mainly preserved, presumably as a consequence of the plausible intracellular phosphotyrosine phosphatase inhibition by angiotensin II.
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PMID:Protein tyrosine phosphatase inhibition by angiotensin II in rat pheochromocytoma cells through type 2 receptor, AT2. 750 23

We characterized inhibition of N-type Ca2+ and M current K+ channels in rat superior cervical ganglion neurons by angiotensin II (angioII) using the patch clamp. Of 120 neurons, 97 showed inhibition of ICa (mean 32%), which was slow in onset and very slow to reverse under whole-cell recording conditions. This inhibition was blocked by the AT1 receptor antagonist losartan, attenuated by inclusion of 2 mM GDP-beta-S in the pipette, mostly pertussis toxin insensitive, half-sensitive to N-ethylmaleimide, and wholly voltage independent. With 20 mM instead of 0.1 mM BAPTA in the pipette, the inhibition was strongly attenuated; however, we detected no angioII-induced [Ca2+]i signal using the fluorescent indicator indo-1. IBa from cell-attached patches was reduced by bath-applied angioII (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M currents were inhibited by angioII in 8 of 11 neurons (mean 50%) cultured overnight. Hence, a second agonist, angioII, may share the slow, second messenger-utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic agonists.
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PMID:Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteins. 751 87

Bovine fasciculata cells in culture (BAC) express both AT1 and AT2 angiotensin receptors. The role and signaling pathways of this latter receptor are still the subject of debate. We found that in BAC stimulation of cortisol (F) production by angiotensin II (A II) is accounted for by both receptor subtypes. We have investigated the potential AT2 signalling pathways involved in this response. As previously described in other cells, we found this receptor to mediate inhibition of ANP stimulated cGMP production through a phosphodiesterase independent pathway. This phenomenon does however not appear to be involved in cortisol production as this response was not affected by the addition of 8-Br-cGMP or ANP. It was however abolished after down-regulation of PKC by phorbol esters, but not by Gi inhibition with pertussis toxin. Moreover and as opposed to the AT1 mediated response, AT2 receptor stimulation potentiated K+ induced F production. In conclusion, these observations suggest that the AT2 pathway which mediates F production requires intact PKC and might involve a Gi independent stimulation of Ca++ or K+ channels.
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PMID:Stimulation of cortisol production through angiotensin AT2 receptors in bovine fasciculata cells. 758 79

The presence of specific AII receptors in 6 different human neuroblastoma cell lines was investigated using binding, cAMP and [Ca2+]i studies. We found high affinity (0.1 nM), low capacity ((1-2).10(3) sites/cell) binding sites for [125I](Sar-1,Ile-8)AII in one half of the cell lines studied. In the positive cell lines mathematical modeling of multiple competition curves among AII and analogs strongly indicated the presence of a homogenous class of sites, i.e., AT1 receptors. The presence of AT1 receptors was further substantiated by AII-induced inhibition of VIP-stimulated cAMP levels and by AII-evoked [Ca2+]i transient. The density of AT1 receptors in neuroblastoma cells was not affected by treatment with pertussis toxin and retinoic acid but was significantly increased by subacute treatment with VIP. In neuroblastoma cells, AII does not stimulate DNA synthesis, suggesting other roles rather than mitogenesis. Neuroblastoma cells represents an interesting model to investigate the function of AII in neural crest derived tissues.
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PMID:Identification and characterization of functional angiotensin II receptors in human neuroblastoma cells. 765 93


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