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

Angiotensin II (AII) receptor subtypes and their potential coupling mechanisms were studied using recently developed peptide and nonpeptide antagonists in rat and bovine adrenal zona glomerulosa cells, as well as in membranes prepared from rat and bovine adrenal cortex and medulla. Comparison of the potencies of these novel antagonists to displace 125I-[Sar1,Ile8]AII from its binding sites revealed two distinct AII binding sites in membranes prepared from rat adrenal capsules (zona glomerulosa) and from rat adrenal inner zones containing the medulla. About 85% of the binding sites of the glomerulosa zone and 30% of those of the inner zones were of the AT1 subtype, with relative affinities for the nonpeptide antagonists Dup 753 and PD 123177 and the peptide antagonist CGP 42112A in the order of Dup 753 much greater than CGP 42112A greater than PD 123177. In contrast, the relative binding potencies for the other (AT2) population of binding sites were CGP 42112A greater than PD 123177 much greater than Dup 753. Neither AII nor its peptide antagonist [Sar1,Ile8]AII could distinguish between the two sets of binding sites. The effects of the new antagonists on functional responses of rat adrenal glomerulosa cells demonstrated that both AII-stimulated aldosterone production and the AII-induced inhibition of adrenocorticotropic hormone-stimulated cAMP formation were mediated by the AT1 receptor subtype. In bovine adrenals, only AT1 receptors were detected in membranes prepared from the cortex and the medulla, as well as in cultured glomerulosa cells. The relative inhibitory potency of Dup 753 was lower by an order of magnitude at bovine than at rat AT1 receptors. The inhibition of AII-induced aldosterone production by the various antagonists was closely correlated with their inhibitory potencies on 125I-[Sar1,Ile8]AII binding to bovine glomerulosa cells. These data suggest that the known effects of AII in adrenal glomerulosa cells are mediated through the AT1 receptor subtype and that the distribution and/or specificity of the AT2 receptors shows marked species variations.
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PMID:Angiotensin II receptor subtypes and biological responses in the adrenal cortex and medulla. 165 13

In dispersed rabbit adrenocortical glomerulosa cells, a non-peptide angiotensin II (AT1) receptor antagonist, CV-11974 (10(-10)-10(-5) M), competitively inhibited angiotensin II- or angiotensin III-stimulated aldosterone production, whereas PD123177, an angiotensin AT2 receptor antagonist, did not. CV-11974 inhibited aldosterone production induced by 4 mM K+ but not by 12 mM K+. CV-11974 had no effect on adrenocorticotropic hormone-stimulated aldosterone or corticosterone production, but inhibited angiotensin II-stimulated corticosterone production. In the rat, TCV-116, the prodrug of CV-11974, (0.1 and 1 mg/kg, p.o.) markedly reduced the elevation of both plasma aldosterone concentration and blood pressure induced by i.v. infusion of angiotensin II. In spontaneously hypertensive rats, TCV-116 at daily p.o. doses of 0.1, 1 and 10 mg/kg for 2 weeks caused a dose-dependent reduction of blood pressure and plasma aldosterone concentration without affecting plasma corticosterone. Thus, TCV-116 inhibited the induction of aldosterone production by not only exogenous but also endogenous angiotensin II.
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PMID:Effect of an angiotensin II receptor antagonist, CV-11974, and its prodrug, TCV-116, on production of aldosterone. 801 47

We have characterized a specific binding site for angiotensin IV on bovine aortic endothelial cell membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.71; average of two experiments that yielded values of 0.71 and 0.72 nM). The binding site is saturable and relatively abundant with a maximal binding capacity of 0.59 pmol/mg protein (average of two experiments that yielded values of 0.39 and 0.78 pmol/mg of protein). Non-equilibrium kinetic analyses at 37 degree C revealed a calculated Kd of 59 pM (average of two experiments that yielded values of 67 and 50 pM). The binding site displays a high affinity for angiotensin receptors AT1 or AT2. An analysis of specificity showed that the binding site displays a high affinity for angiotensin IV, low affinities for angiotensin II, [Sar1, Val5, Ala8]angiotensin II and does not recognize L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'-(1 H-tetrazole-5-yl)[1,1'-biphenyl]-4-yl)methyl]-3H-imidazo[4, 5-beta]pyridine H2O) and PD 123319 (1-[4-dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl) 4,5,6,7-tetrahydro-1 H-imidazo[4,5-c]pyridine-6-carboxylic acid). A few unrelated hormones (bradykinin, [Arg8] vasopressin, endothelin-1, atrial natriuretic factor, isoproterenol and adrenocorticotropic hormone) were unable to inhibit any 125I-angiotensin IV binding. The affinities of different structural analogues of angiotensin IV revealed that the N-terminal position is critical for receptor recognition and the C-terminal proline is also important. GTP gamma S and polyvinyl sulfate did not affect the binding, suggesting that the receptor is not coupled to a G-protein. The divalent cations Mg2+ and Ca2+ were shown to diminish the binding of 125I-angiotensin IV. Cross-linking of 125I-angiotensin IV to bovine aortic endothelial cell membranes in the presence of disuccinimidyl suberate, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a major band of 186 +/- 12 kDa. The presence in high concentration of this angiotensin binding site on aortic endothelial cells suggest the existence of a novel mechanism involved in the control of vascular tone or vascular permeability.
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PMID:Characterization of a binding site for angiotensin IV on bovine aortic endothelial cells. 856 70

We previously reported that brain angiotensin II type 2 (AT2) receptors contribute to the hyperthermia induced by intrahypothalamic (intrapreoptic (i.p.o.)) administration of prostaglandin E2 (PGE2) in rats. The present study was carried out to investigate the role of angiotensin II (ANG II) receptors in the cardiovascular and adrenocorticotropic hormone (ACTH) responses induced in rats by i.p.o. injection of PGE2. PGE2 (100 ng) produced marked increases in blood pressure, heart rate, and plasma ACTH concentration. These changes were significantly enhanced by i.p.o. treatment with an AT1-receptor antagonist, losartan, while an AT2-receptor antagonist, CGP 42112A, had no effect. In contrast, losartan, but not CGP 42112A, reduced the pressor and ACTH responses to i.p.o. injection of a large dose of "exogenous" ANG II (25 ng). These results suggest that while "endogenous" ANG II exerts inhibitory effects on both the cardiovascular and the ACTH responses to i.p.o. PGE2 by way of preoptic AT1-receptors, a large dose of exogenous ANG II produces effects opposite to those induced by the endogenous ANG II that is released locally and in small amounts by i.p.o. PGE2.
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PMID:Angiotensin AT1 receptors in the preoptic area negatively modulate the cardiovascular and ACTH responses induced in rats by intrapreoptic injection of prostaglandin E2. 1066

With increasing case reports, it has been indicated that some cases with adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) show abnormal responses in cortisol to various stimulation tests. Here we report a case of AIMAH that showed an aberrant response to angiotensin II via AT1 receptor in cortisol hypersecretion. A 53-yr-old man was admitted to our division seeking further examinations for the possible diagnosis of Cushing's syndrome. He had hypertension, diabetes mellitus, and physical stigmata, such as moon face and central obesity. His plasma ACTH level was undetectable, and plasma cortisol level was high. Plasma cortisol showed no normal diurnal rhythm and was not suppressed after the administration of 8 mg of dexamethasone. Abdominal computed tomography demonstrated nodular enlargement of bilateral adrenal glands. He was diagnosed with Cushing's syndrome owing to AIMAH. An injection of arginine vasopressin (AVP) increased plasma cortisol and aldosterone levels, whereas ACTH remained undetectable. After 4 h in an upright position, plasma cortisol and aldosterone levels were increased. Pretreatment with candesartan, angiotensin II receptor AT1 antagonist, blocked the increase in plasma cortisol level. These results suggested a possibility of adrenal hypersensitivity to angiotensin II and AVP in cortisol secretion. Bilateral laparoscopic adrenalectomy was performed. The histological findings of the specimen were compatible with AIMAH. In summary, we have made the first report on a case of AIMAH with possible hypersensitivity to angiotensin II.
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PMID:Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with possible adrenal hypersensitivity to angiotensin II. 1157 27

Ataxia-telangiectasia (AT) syndrome (cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, susceptibility to infections, and neoplasia) is associated with cyto- and nucleomegaly in several organ systems. Our aim was to determine (1) whether such cellular abnormalities in the pituitary selectively involve specific cell types, and (2) the proliferation and DNA ploidy status of such cells. Three AT autopsy pituitaries were studied by histology, immunohistochemistry (pituitary hormones, MIB-1, p53 protein), in situ hybridization (pituitary hormones), and Feulgen stain image analysis for ploidy. Results indicated that, in adenohypophyses the scattered pleomorphic, bizarre nuclei were mainly those of somatotrophs and corticotrophs, growth hormone (GH), or adrenocorticotropic hormone (ACm) immunoreactive and expressing the GH or ACTH gene, respectively. Cyto- and nucleomegaly were less frequent in other secretory cells but were also noted in pituicytes of the posterior lobe. Affected cells were immunonegative for MIB-1 and for p53 protein. Image morphometric DNA analysis showed the bizarre cells to be aneuploid with complex histogram patterns, including many nuclei with DNA contents >8 n. No adenomas were found. We conclude that in AT adenohypophyseal cells with cyto- and nucleomegaly, as well as pleomorphism, synthesize and store adenohypophyseal hormones, mainly GH or ACTH. They and affected pituicytes are nonproliferative and are aneuploid.
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PMID:Pituitary Changes in Ataxia-Telangiectasia Syndrome: An Immunocytochemical, In Situ Hybridization, and DNA Cytometric Study of Three Cases. 1211 23

Bovine adrenocortical cells express bTREK-1 K+ channels that set the resting membrane potential (V(m)) and couple angiotensin II (AngII) and adrenocorticotropic hormone (ACTH) receptors to membrane depolarization and corticosteroid secretion. In this study, it was discovered that AngII inhibits bTREK-1 by separate Ca2+- and ATP hydrolysis-dependent signaling pathways. When whole cell patch clamp recordings were made with pipette solutions that support activation of both Ca2+- and ATP-dependent pathways, AngII was significantly more potent and effective at inhibiting bTREK-1 and depolarizing adrenal zona fasciculata cells, than when either pathway is activated separately. External ATP also inhibited bTREK-1 through these two pathways, but ACTH displayed no Ca2+-dependent inhibition. AngII-mediated inhibition of bTREK-1 through the novel Ca2+-dependent pathway was blocked by the AT1 receptor antagonist losartan, or by including guanosine-5'-O-(2-thiodiphosphate) in the pipette solution. The Ca2+-dependent inhibition of bTREK-1 by AngII was blunted in the absence of external Ca2+ or by including the phospholipase C antagonist U73122, the inositol 1,4,5-trisphosphate receptor antagonist 2-amino-ethoxydiphenyl borate, or a calmodulin inhibitory peptide in the pipette solution. The activity of unitary bTREK-1 channels in inside-out patches from adrenal zona fasciculata cells was inhibited by application of Ca2+ (5 or 10 microM) to the cytoplasmic membrane surface. The Ca2+ ionophore ionomycin also inhibited bTREK-1 currents through channels expressed in CHO-K1 cells. These results demonstrate that AngII and selected paracrine factors that act through phospholipase C inhibit bTREK-1 in adrenocortical cells through simultaneous activation of separate Ca2+- and ATP hydrolysis-dependent signaling pathways, providing for efficient membrane depolarization. The novel Ca2+-dependent pathway is distinctive in its lack of ATP dependence, and is clearly different from the calmodulin kinase-dependent mechanism by which AngII modulates T-type Ca2+ channels in these cells.
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PMID:Angiotensin II inhibits bTREK-1 K+ channels in adrenocortical cells by separate Ca2+- and ATP hydrolysis-dependent mechanisms. 1599 19

This study determined the long-term influence of prenatal nicotine exposure (PN) on blood pressure and vascular functions in the aged offspring rats. PN did not affect body weight and plasma adrenocorticotropic hormone level; however, it significantly reduced plasma angiotensin I and angiotensin II in both sexes. Systolic pressure in the male aged PN offspring was significantly higher. Angiotensin II-increased mean arterial pressure was higher in the aged PN offspring than that in the control regardless of sex. AT1 receptor blocker losartan, not AT2 receptor antagonist PD123319, reduced blood pressure in the aged PN rats more than that in the control. In the aged PN offspring, angiotensin II-increased vessel contraction and intracellular calcium level were higher in small mesenteric arteries. Acetylcholine-mediated vascular relaxation was weaker, and nitric oxide-related endothelial functions were damaged in aortic rings of PN offspring. Thickness of the wall of mesenteric arteries was increased in the male aged PN offspring. Ratio of AT1/AT2 receptors was significantly increased in the vessel of the PN group regardless of sex. These data provide new information on the very long term influence of PN on vascular structures and functions in the aged offspring, demonstrate that the aged PN female rats were not free of vascular risks after menopause, and suggest that multiple pathways may be involved in the detrimental alterations of the cardiovascular system of the PN rats.
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PMID:Angiotensin II-mediated vascular changes in aged offspring rats exposed to perinatal nicotine. 2350 May 20