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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific and high affinity binding sites for angiotensin II were demonstrated in the anterior pituitary gland by binding studies with [125I] iodoangiotensin II. The binding properties of the pituitary receptors were similar to those of angiotensin II receptors present in the adrenal gland. The concentration of binding sites in rat anterior pituitary (293 +/- 50 fmoles/mg protein) was less than in the adrenal gland, but was much greater than in smooth muscle. Angiotensin II receptors were identified in the anterior pituitary tissue of mature and immature animals of both sexes, and in species including rat, rabbit and dog. No binding of angiotensin II was detected in posterior pituitary homogenates, or in GH3 pituitary tumor cells. Collagenase-dispersed anterior pituitary cells also contained specific binding sites for angiotensin II, with equilibrium binding constant (Ka) of 3.6 x 10(9) M-1. The presence of specific high-affinity angiotensin II receptor in the anterior pituitary gland provides a mechanism by which angiotensin-like peptides could modulate the process of pituitary hormone secretion.
Mol Cell Endocrinol 1982 Feb
PMID:Characterization of angiotensin II receptors in the anterior pituitary gland. 627 51

Angiotensin II binding sites in a rabbit ventricular myocardial particulate fraction were identified and characterized with the radioligand 125I-angiotensin II. The order of potency in competing with 125I-angiotensin II for these sites was similar to that observed in physiological studies. Computer-assisted analysis of the competition of binding sites for 0.3 nM 125I-angiotensin II by unlabeled angiotensin II (3 X 10(-11) M to 1 X 10(-5) M) demonstrated that optimal fitting of the competition curves was attained with a two-site model having one site of high affinity (KA1 = 2.4 +/- 0.6 X 10(9) M-1), low capacity (N1 = 7.8 +/- 0.8 fmoles/mg of protein) and a second site low affinity (KA2 = 9.6 +/- 0.6 X 10(6) M-1) and high capacity (N2 = 219 +/- 128 fmoles/mg of protein). Analysis of competition by Sar1-Ile8 angiotensin II for 125I-angiotensin II binding sites indicated that the antagonist interacted with the first site with high affinity (KA1 = 8 X 10(9) M-1), but interacted minimally with the second site (KA2 = 10(5) M-1). Monovalent cations (Na+, K+, Li+, NH4+) were roughly equipotent in decreasing 125I-angiotensin II binding by reducing the number of high-affinity sites (N1 = 2.6 +/- 0.7 fmoles/mg of protein with 100 mM Na+) without changing the affinity of either site or the number of low-affinity sites. The number of high-affinity sites was increased to 14.4 +/- 1.5 fmoles/mg of protein by 5 mM Mg2+. In the presence of divalent cations, nucleotides reduced binding of 125I-angiotensin II with the potency order guanosyl-5'-yl-imidodiphosphate greater than GTP greater than GDP greater than ATP greater than GMP. Guanosyl-5'yl-imidodiphosphate significantly reduced the affinity of the high-affinity site (KA1 = 1.0 +/- 0.2 X 10(9) M-1) and perhaps of the low-affinity site (KA2 = 1.0 +/- 2.2 X 10(6) M-1). Computer-assisted assessment of dissociation of 0.3 nM 125I-angiotensin II from rabbit myocardial membranes corroborated the equilibrium data: dissociation was biphasic (K-1 = 0.19 +/- 0.2 min-1 for a rapidly dissociating site, k-1 = 2.5 +/- 2.1 X 10(-3) min-1 for a slowly dissociating site); 5 mM Mg2+ did not significantly change either dissociation rate; but guanosyl-5'-yl-imidodiphosphate significantly increased dissociation rates from both sites. Despite the indirect evidence that these angiotensin II receptors interact with guanine nucleotide regulatory proteins, angiotensin II (10(-6) M) failed to influence adenylate cyclase activity. The physiological implications of the presence in ventricular myocardium of two distinct angiotensin II receptors and in particular the implications of a receptor-associated guanine nucleotide regulatory protein which does not couple to adenylate cyclase require further investigation.
Mol Pharmacol 1983 Sep
PMID:Characterization of the rabbit ventricular myocardial receptor for angiotensin II. Evidence for two sites of different affinities and specificities. 631 Mar 63

We have previously shown that angiotensin II (AII) is a mitogen for neonatal rat cardiac fibroblasts. However, the signaling events that lead to fibroblast cell growth in response to AII remain to be elucidated. Mitogen-activated protein (MAP) kinases are cytosolic serine/threonine kinases which have been shown to be activated in quiescent cells by diverse growth stimuli, thereby being linked to growth regulatory pathways. This study was designed to determine whether MAP-kinase activation occurred in response to AII/receptor coupling in neonatal rat cardiac fibroblasts and the role of MAP-kinase activation in the AII-induced proliferation of these cells. Immunoblot analysis of MAP-kinase isoforms revealed predominantly p44 with less p42 MAP-kinase in rat cardiac fibroblasts. Both isoforms were activated upon stimulation of the cells with AII for 5 min or platelet derived growth factor-BB for 10 min. Angiotensin II stimulated MAP-kinase in a dose-dependent fashion with an EC50 of 2.5 nM. Two minutes following stimulation with 1 microM AII MAP-kinase activity increased from 90 +/- 17.9 to 477.5 +/- 75.9 pmol/min/mg protein, P < 0.05, n = 4. A smaller, sustained, secondary increase in MAP-kinase activity from 37.7 +/- 5.3 to 110.9 +/- 15.3 pmol/min/mg protein, P < 0.05, n = 4, was observed in response to AII between 120-150 minutes following receptor occupancy. The responses to AII were markedly attenuated by the AT1 receptor antagonist EXP3174. Stimulation of the cells with carbachol induced the first but not the second phase of MAP-kinase activity and this compound had no effect on cellular growth. The second phase of MAP-kinase activity 2-2.5 h after AII stimulation, paralleled data demonstrating that a 2-3 h receptor occupancy with AII was necessary to induce DNA synthesis and fibroblast proliferation. These results indicate that AII stimulates a biphasic activation of MAP-kinase by the AT1 receptor and that this pathway may participate in the AII induced mitogenic response in cardiac fibroblasts.
J Mol Cell Cardiol 1995 May
PMID:Angiotensin II is a potent stimulator of MAP-kinase activity in neonatal rat cardiac fibroblasts. 747 73

Angiotensin II (AII) is a growth factor that stimulates protein synthesis and induces cellular hypertrophy in aortic smooth muscle cells (SMC). This trophic effect is mediated by the AT1 subtype of AII receptors. However, very little is known about the cellular signaling pathways involved in this response. In the present study, we examined the role of protein tyrosine phosphorylation in the growth-promoting effects of AII on rat aortic SMC. The addition of AII to quiescent aortic SMC induced tyrosine phosphorylation of multiple substrates, as revealed by antiphosphotyrosine immunoblotting. This response was blocked by preincubation with the AT1-selective antagonist losartan. To explore the functional role of this signaling pathway, we performed experiments with two mechanistically distinct tyrosine kinase inhibitors. Treatment of quiescent aortic SMC with genistein and herbimycin A abolished the stimulatory effect of AII on overall protein tyrosine phosphorylation. Similarly, the two inhibitors prevented AII-induced tyrosine phosphorylation of the cytoskeletal protein paxillin. Under the same conditions, incubation with genistein or herbimycin A did not interfere with AII binding to the AT1 receptor and did not significantly affect AII-stimulated inositol-1,4,5-trisphosphate production and Ca2+ mobilization. In parallel to their selective action on tyrosine phosphorylation, both genistein and herbimycin A completely inhibited AII-stimulated protein synthesis in a dose-dependent manner. In contrast, the two inhibitors were much less potent in preventing the trophic effect of phorbol-12-myristate 13-acetate in these cells. We further demonstrate that genistein and herbimycin A did not prevent mitogen-activated protein kinase activation and c-fos gene induction, which is consistent with the notion that these downstream effectors do not link AII-induced tyrosine phosphorylation to protein synthesis. These results provide evidence that tyrosine phosphorylation has a critical role in cellular hypertrophy and is involved in AII action in vascular SMC.
Mol Pharmacol 1995 Oct
PMID:Involvement of a tyrosine kinase pathway in the growth-promoting effects of angiotensin II on aortic smooth muscle cells. 747 82

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.
Mol Endocrinol 1995 Aug
PMID:Modulation of a Ca(2+)-activated K+ channel by angiotensin II in rat adrenal glomerulosa cells: involvement of a G protein. 747 91

Rat aortic smooth muscle cells produced large quantities of nitric oxide (NO) after exposure to interleukin-1 beta, and this was depressed in the presence of the protein kinase C inhibitor bisindolylmaleimide. Intracellular cAMP levels were elevated mildly in cytokine-treated smooth muscle cells, and the presence of forskolin enhanced both the cAMP levels and NO production. Inhibition of GTP:cyclohydrolase I by 2,4-diamino-6-hydroxypyrimidine attenuated NO production by interleukin-1 beta-treated cells. GTP:cyclohydrolase is the regulatory enzyme for de novo tetrahydrobiopterin synthesis, and the latter is a required cofactor for NO synthase activity. Treatment of smooth muscle cells with forskolin induced GTP:cyclohydrolase mRNA expression, and simultaneous treatment of cells with forskolin and phorbol esters elicited NO production. Angiotensin II and arginine-vasopressin, acknowledged agonists for protein kinase C, elicited production of NO by forskolin-treated smooth muscle cells. These observations confirm the importance of GTP:cyclohydrolase activity for NO production by cultured smooth muscle cells and implicate both adenylyl cyclase and protein kinase C in this process.
Mol Pharmacol 1994 Aug
PMID:Simultaneous activation of adenylyl cyclase and protein kinase C induces production of nitric oxide by vascular smooth muscle cells. 752 13

In GN4 rat liver epithelial cells, angiotensin II (Ang II) and other agonists which activate phospholipase C stimulate tyrosine kinase activity in a calcium-dependent, protein kinase C (PKC)-independent manner. Since Ang II also produces a proliferative response in these cells, we investigated downstream signaling elements traditionally linked to growth control by tyrosine kinases. First, Ang II, like epidermal growth factor (EGF), stimulated AP-1 binding activity in a PKC-independent manner. Because increases in AP-1 can reflect induction of c-Jun and c-Fos, we examined the activity of the mitogen-activated protein (MAP) kinase family members Erk-1 and -2 and the c-Jun N-terminal kinase (JNK), which are known to influence c-Jun and c-Fos transcription. Ang II stimulated MAP kinase (MAPK) activity but only approximately 50% as effectively as EGF; again, these effects were independent of PKC. Ang II also produced a 50- to 200-fold activation of JNK in a PKC-independent manner. Unlike its smaller effect on MAPK, Ang II was approximately four- to sixfold more potent in activating JNK than EGF was. Although others had reported a lack of calcium ionophore-stimulated JNK activity in lymphocytes and several other cell lines, we examined the role of calcium in GN4 cells. The following results suggest that JNK activation in rat liver epithelial cells is at least partially Ca(2+) dependent: (i) norepinephrine and vasopressin hormones that increase inositol 1,4,5-triphosphate stimulated JNK; (ii) both thapsigargin, a compound that produces an intracellular Ca(2+) signal, and Ca(2+) ionophores stimulated a dramatic increase in JNK activity (up to 200-fold); (iii) extracellular Ca(2+) chelation with ethylene glycol tetraacetic acid (EGTA) inhibited JNK activation by ionophore and intracellular chelation with 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl-ester (BAPTA-AM) partially inhibited JNK activation by Ang II or thapsigargin; and (iv) JNK activation by Ang II was inhibited by pretreatment of cells with thapsigargin and EGTA, a procedure which depletes intracellular Ca(2+) stores. JNK activation following Ang II stimulation did not involve calmodulin; either W-7 nor calmidizolium, in concentrations sufficient to inhibit Ca(2+)/calmodulin-dependent kinase II, blocked JNK activation by Ang II. In contrast, genistein, in concentrations sufficient to inhibit Ca(2+)-dependent tyrosine phosphorylation, prevented Ang II and thapsigargin-induced JNK activation. In summary, in GN4 rat liver epithelial cells, Ang II stimulates JNK via a novel Ca(2+)-dependent pathway. The inhibition by genistein suggest that Ca(2+)-dependent tyrosine phosphorylation may modulate the JNK pathway in a cell type-specific manner, particularly in cells with a readily detectable Ca(2+)-regulated tyrosine kinase.
Mol Cell Biol 1995 Nov
PMID:Angiotensin II stimulates calcium-dependent activation of c-Jun N-terminal kinase. 756 68

Subtypes of the angiotensin II (Ang II) type-1 (AT1) receptor are probably involved in distinct actions of the peptide, since their distribution in peripheral organs and regulation of their gene expression are different. We investigated the distribution of AT1A and AT1B receptor subtype mRNAs in the rat forebrain and pituitary using sensitive cRNA probes for in situ hybridization. High level of AT1A receptor mRNA expression is observed in the subfornical organ (SFO) and in the anterior hypothalamus, particularly the periventricular tissue surrounding the anterior portion of the 3rd ventricle (AV3V), which contains the organum vasculosum of the lamina terminalis (OVLT), the median preoptic nucleus and the preoptic periventricular nucleus as well as in the hypothalamic periventricular nucleus and in the parvocellular part of the paraventricular nucleus (PVN). Moderate to strong AT1A labeling was found in the anterior olfactory nucleus, the piriform cortex and the nucleus of the lateral olfactory tract. Very low AT1B receptor mRNA expression was found in the SFO and the PVN. In contrast, strong AT1B receptor mRNA expression coincided with low AT1A receptor mRNA expression in the anterior pituitary. Labeling was cytoplasmic at the light microscopic level. We thus suggest that the AT1A receptor is responsible for the central actions of Ang II in the rat forebrain whereas direct actions of Ang II on the anterior pituitary are mediated by the AT1B receptor subtype.
Brain Res Mol Brain Res 1995 May
PMID:The angiotensin receptor subtype AT1A predominates in rat forebrain areas involved in blood pressure, body fluid homeostasis and neuroendocrine control. 760 44

Angiotensin II (AGII) and thromboxane A2 (TXA2), potent vasoconstrictors, augmented the production of the precursor of tissue procollagenase/promatrixmetalloproteinase-1 (proMMP-1) and DNA synthesis in cultured human aortic smooth muscle cells (SMC) significantly compared with that in untreated SMC. Moreover, AGII and TXA2 stimulated hydrolysis of phosphoinositides and subsequent formation of inositol triphosphate (IP3), leading to an increase in the intracellular free Ca2+ concentration. These results suggest that the production of proMMP-1 increased by AGII and TXA2 in intimal SMC in relation to cell proliferation plays a role in arterial reconstruction in vascular diseases.
Biochem Mol Biol Int 1995 Feb
PMID:Effect of angiotensin II and thromboxane A2 on the production of matrix metalloproteinase by human aortic smooth muscle cells. 766 80

We previously reported that angiotensin II (Ang II) increases cGMP content through a new Ang II receptor subtype that is distinct from both the AT1 and AT2 subtypes in differentiated Neuro-2A cells. In this study, the mechanism of the Ang II-stimulated cGMP increase was investigated in comparison with bradykinin- and atrial natriuretic factor (ANF)-stimulated cGMP increases in differentiated Neuro-2A cells. Ang II increased cGMP in differentiated Neuro-2A cells rapidly, with a maximal effect in 30 sec and a return to basal levels in 60 sec. Removal of extracellular Ca2+ or pretreatment with a membrane-permeable Ca2+ chelator [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester] attenuated Ang II-stimulated cGMP accumulation. Both the time course and Ca2+ dependency of the effect of Ang II were similar to those of the effect of bradykinin, which activates soluble guanylyl cyclase, but distinct from those of the effect of ANF, which activates particulate guanylyl cyclase. Methylene blue, an inhibitor of soluble guanylyl cyclase, attenuated the effects of Ang II and bradykinin but not that of ANF. LaCl3, a nonspecific Ca2+ blocker, prevented Ang II-stimulated cGMP accumulation. L-type Ca2+ channel blockers, nifedipine and diltiazem, or an N-type Ca2+ channel blocker, omega-conotoxin, failed to inhibit the effect of Ang II. Ang II had no effect on formation of 1,4,5-inositol trisphosphate or cAMP content, whereas bradykinin stimulated 1,4,5-inositol trisphosphate formation in differentiated Neuro-2A cells. Further, the nitric oxide synthase inhibitors NG-monomethyl-L-arginine and NG-nitro-L-arginine attenuated Ang II- and bradykinin-stimulated elevation of cGMP content but not that stimulated by ANF. The Ca2+ ionophore A23187 also stimulated cGMP formation and the effect was inhibited by the nitric oxide synthase inhibitors. These results indicate that the newly found Ang II receptor mediates cGMP formation through activation of soluble guanylyl cyclase and that the activation is mediated by nitric oxide, which is increased by Ca2+ influx via an ion channel distinct from the L-type and N-type Ca2+ channels.
Mol Pharmacol 1993 Apr
PMID:New signaling mechanism of angiotensin II in neuroblastoma neuro-2A cells: activation of soluble guanylyl cyclase via nitric oxide synthesis. 768 50


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