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

We have previously shown that sodium restriction upregulates the genes encoding angiotensin II receptor (AT1) subtypes, AT1A and AT1B, in the adrenal gland and that this upregulation is mediated by activation of the AT1 receptor. There are multiple interactions between the renin-angiotensin and the adrenergic nervous systems; thus, we conducted the present experiment to investigate whether low sodium-induced upregulation of adrenal AT1A and AT1B is modulated by the alpha1-adrenoreceptor. Seven-week-old male Wistar rats were divided into four groups and given normal sodium diet (0.5%, NS), NS+prazosin (3.5 microg x kg(-1) x min(-1) by osmotic pump), low sodium diet (0.07%, LS), or LS+prazosin. Body weight and mean arterial pressure were not modified over the 2 weeks of treatment (P>.05). Pressor responses to bolus injection of the alpha1-agonist phenylephrine were inhibited in both prazosin groups, compared with NS and LS rats (P<.05). Adrenal AT1A mRNA, determined by Northern blot analysis, was increased in LS (P<.05) but not in NS+prazosin (P>.05), compared with NS. Prazosin enhanced the LS-induced increase of AT1A mRNA (P<.05). Adrenal AT1B mRNA was increased in both LS and NS+prasozin rats, compared with NS rats (P<.05). Prazosin also enhanced the LS-induced increase in AT1B mRNA (P<.05). Therefore, blockade of alpha1-adrenoreceptor results in an enhancement of LS-induced upregulation of adrenal mRNA for AT1A and AT1B. These data suggest that the sympathetic nervous system exerts an inhibitory action, via activation of the alpha1-adrenoreceptor, on AT1A and AT1B gene expression in the adrenal gland during sodium depletion.
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PMID:Regulation of type 1 angiotensin II receptor in adrenal gland: role of alpha1-adrenoreceptor. 931 15

Angiotensin II acts on at least two receptor subtypes, AT1 and AT2. Although the physiological role of the AT2 receptor is still poorly defined, it may be implicated in inhibition of cell growth, vasorelaxation, and apoptosis. In the present study, to investigate the role of the AT2 receptor in the kidney and its implication in hypertensive states, we examined its expression using cultured mesangial cells (MC) from normotensive Wistar-Kyoto rats (WKY) and from stroke-prone spontaneously hypertensive rats (SHRSP). Receptor binding assays were performed using a nonselective ligand, [Sar1,Ile8]angiotensin II, or AT2-selective CGP42112A. Binding assays revealed that MC from WKY exhibited both AT1 and AT2 receptors, the ratio of which was confluence-dependent. In contrast, MC from SHRSP, whose proliferation activity was much higher than those from WKY, showed only the AT1 subtype. In receptor binding and Northern blot analyses, expression of the AT2 receptor of WKY-MC was low in the growing state but significantly induced upon confluence to become abundant in the post-confluent state, whereas that of SHRSP-MC was undetectable in either state. Gene expressions of AT1A and AT1B receptors were not significantly altered in either strain during the time in culture. These results indicate that the mesangial AT2-receptor expression is growth-dependent and suggest a role in the inhibition of MC growth in WKY. Much lower expression of the AT2 receptor in MC from SHRSP may suggest involvement in their higher proliferation activity and possibly in consequent renal disorders.
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PMID:Growth-dependent induction of angiotensin II type 2 receptor in rat mesangial cells. 931 17

Brain angiotensin II (Ang II) inhibits pituitary prolactin release by an indirect mechanism requiring stimulation of dopamine formation and release. We report that [125I]Sar1-Ang II binding to AT1 receptors and AT1A receptor mRNA expression increase selectively in the dorsomedial arcuate nucleus of 17beta-estradiol-primed ovariectomized rats after treatment with progesterone. In hormone-treated rats, arcuate nucleus AT1A receptor mRNA expression is associated with tyrosine hydroxylase-positive neurons. No AT1A receptor mRNA was detected in tyrosine hydroxylase-positive cells of the arcuate nucleus of intact male rats. Conversely, in the anterior pituitary, where local or circulating Ang II stimulates prolactin release, [125I]Sar1-Ang II binding to AT1 receptors and AT1B receptor mRNA expression are decreased in 17beta-estradiol/progesterone-treated ovariectomized rats. Thus, AT1A receptors in the dorsal arcuate nucleus and AT1B receptors in the anterior pituitary are regulated inversely by estrogen/progesterone treatment, supporting the hypothesis of a dual role for brain and pituitary Ang II on prolactin release. The colocalization of AT1A receptor mRNA and tyrosine hydroxylase in neurons of the arcuate nucleus furthermore indicates that within this area central Ang II acts directly on dopaminergic neurons. These results support the hypothesis that central Ang II inhibits pituitary prolactin release indirectly via modulation of dopaminergic activity in the arcuate nucleus.
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PMID:Angiotensin II AT1A receptor mRNA expression is induced by estrogen-progesterone in dopaminergic neurons of the female rat arcuate nucleus. 933 3

The discovery that all components of the renin-angiotensin system (RAS) are present in the central nervous system led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurons have been visualized in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular nucleus, and supraoptic nucleus, and a second pathway connecting the hypothalamus to the medulla oblongata. Blood-brain barrier deficient circumventricular organs are rich in angiotensin II receptors. By activating these receptors, circulating angiotensin II may act on central cardiovascular centers via angiotensinergic neurons, providing a link between peripheral and central angiotensin II systems. Among the effector peptides of the brain RAS, angiotensin II and angiotensin III have the same affinity for the two pharmacologically well-defined receptors: type 1 (AT1) and type 2 (AT2). When injected in the brain, these peptides increase blood pressure, water intake, and anterior and posterior pituitary hormone release and may modify memory and learning. The cloning of AT1 and AT2 receptor cDNAs has revealed that these receptors belong to the seven transmembrane domain receptor family. In rodents, two AT1 receptor subtypes, AT1A and AT1B, have been isolated. Using specific riboprobes for in situ hybridization histochemistry, recent studies mapped the distribution of AT1A, AT1B, and AT2 receptor mRNAs in the adult rat and found a predominant expression of AT1A and AT2 mRNA in the brain and of AT1B in the pituitary. Very limited overlap was found between the brain expression of AT1A and AT2 mRNAs. In several functional entities of the brain, such as the preoptic region, the hypothalamus, the olivocerebellary system, and the brainstem baroreflex arc, the colocalization of receptor mRNA, binding sites, and angiotensin immunoreactive nerve terminals suggests local synthesis and expression of angiotensin II receptors. In other areas, such as the bed nucleus of the stria terminalis, the median eminence, or certain parts of the nucleus of the solitary tract, angiotensin II receptors are likely of extrinsic origin. The neuronal expression of AT1A and AT2 receptors was demonstrated in the subfornical organ, the hypothalamus, and the lateral septum. By using double label in situ hybridization, AT1A receptor expression was localized in corticotropin releasing hormone but not in vasopressin containing neurons in the hypothalamus. The information is discussed together with functional data concerning the role of brain angiotensins, in an attempt to provide a better understanding of the physiological and functional roles of each receptor subtype.
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PMID:Expression of angiotensin type-1 (AT1) and type-2 (AT2) receptor mRNAs in the adult rat brain: a functional neuroanatomical review. 934 32

The localization of two type 1 angiotensin II receptor subtype mRNA, AT1A and AT1B, was determined by reverse transcription-PCR on microdissected glomeruli and nephron segments. The coupling sensitivity of these two receptor subtypes was evaluated by measuring variations in intracellular calcium ([Ca2+]i) elicited by angiotensin II (Ang II) in structures expressing either AT1A or AT1B mRNA, using Fura-2 fluorescence. The highest expression of AT1 mRNA was found in glomerulus, proximal tubule, and thick ascending limb. In glomerulus, AT1A and AT1B mRNA were similarly expressed, whereas in all nephron segments AT1A mRNA expression was dominant (approximately 84%). The increase in [Ca2+]i elicited by 10(-7) mol/L Ang II was highest in proximal segments (delta [Ca2+]i is approximately equivalent to 300 to 400 nmol/L) and thick ascending limb (delta [Ca2+]i is approximately equivalent to 200 nmol/L). In glomerulus and collecting duct, the response was lower (delta < 100 nmol/L). The median effective concentrations for Ang II were of the same order of magnitude in glomerulus (12.2 nmol/L), in which both AT1A and AT1B are expressed, and in cortical thick ascending limb (10.3 nmol/ L), in which AT1A is almost exclusively expressed. The Ang II-induced calcium responses were totally abolished by the AT1 receptor antagonist losartan (1 mumol/L) but not by the AT2 antagonist PD 123319 (1 mumol/L). In the absence of external Ca2+, the peak phase of the response induced by 10(-7) mol/L Ang II was reduced and shortened, suggesting that a part of the [Ca2+]i increase originated from the mobilization of the intracellular Ca2+ pool. In conclusion, these results demonstrate that in the rat kidney: (1) AT1A is the predominant AT1 receptor subtype expressed in the nephron segments, (2) glomerulus is the only structure with a relatively high AT1B mRNA content, and (3) AT1A and AT1B receptor subtypes do not differ in their efficiency for the activation of calcium second-messenger system.
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PMID:Expression of type 1 angiotensin II receptor subtypes and angiotensin II-induced calcium mobilization along the rat nephron. 935 68

Differential evaluation of angiotensin II (Ang II) receptors (AT1A, AT1B and AT2) expression was performed in dispersed adenohypophyseal cells fractionated by unit gravity sedimentation. Binding of [125I-Sar1-Ile8]-Ang II and its displacement by specific nonpeptidic AT1 (DuP753) and AT2 (PD123319) antagonists was monitored throughout the gradient. Quantification of mRNA levels corresponding to both AT1 receptor subtypes (AT1A and AT1B) was achieved by reverse transcriptase polymerase chain reaction (RT-PCR) amplification in the presence of an AT1 receptor mutant cRNA as internal standard. Fractions were characterised by radioimmunoassay for the five major anterior pituitary hormones and by counting immunocytochemically labelled cells. Quantification of AT1 receptor subtype mRNA levels was also performed in four hypophyseal cell lines secreting prolactin, growth hormone, corticotropin and a gonadotropin subunit. As already described for the whole pituitary, AT1B receptor mRNA is predominantly expressed (80% of total AT1A + AT1B receptor mRNA content), whereas AT1A is expressed at lower level (20%) in dispersed pituitary cells. Most AT1 receptor mRNA and binding co-elute with fractions enriched in lactotropes and corticotropes. In contrast to AT1B, AT1A receptor mRNA is not present in heavier populations of lactotropes or in somatomammotropes. Low AT1B mRNA levels are detected in GH4C1 and in GC cells, two clones which secrete respectively prolactin and growth hormone. In contrast, no AT1 receptor mRNA expression was found in two other cell lines, AtT20 and alphaT3-1, which produce pro-opiomelanocortin and gonadotropin. It is concluded that expression of AT1 receptor subtypes is heterogeneous in different populations of lactotropes and corticotropes.
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PMID:Expression of angiotensin II receptor subtypes AT(1A) and AT(1B) in enriched fractions of dispersed rat pituitary cells. 943 Apr 47

Angiotensin II and angiotensin III in the brain exert their various effects by acting on two pharmacologically well-defined receptors, the type-1 (AT1) and the type-2 (AT2) receptors. Receptor binding autoradiography has revealed the dominant presence of AT1 in brain nuclei involved in cardiovascular, body fluid and neuroendocrine control. The cloning of the AT1 complementary DNA has revealed the existence of two receptor subtypes in rodents, AT1A and AT1B. Using specific riboprobes for in situ hybridization, we have previously shown that the AT1A messenger RNA is predominantly expressed in the rat forebrain; in contrast the AT1B subtype predominates in the anterior pituitary. Using a similar technical approach, the aim of the present study was to establish the precise anatomical localization of cells synthetising the AT1A receptor in the adult rat brain. High AT1A messenger RNA expression was found in the vascular organ of the lamina terminalis, the median preoptic nucleus, the subfornical organ, the hypothalamic periventricular nucleus, the parvocellular parts of the paraventricular nucleus, the nucleus of the solitary tract and the area postrema, in agreement with previous autoradiographic studies, describing a high density of AT1 binding sites in these nuclei. In addition, AT1A messenger RNA expression was detected in several brain areas, where no AT1 binding was reported previously. Thus, we identify strong expression of AT1A messenger RNA expression in scattered cells of the lateral parts of the preoptic region, the lateral hypothalamus and several brainstem nuclei. In none of these structures was the AT1B messenger RNA detectable at the microscopic level. In conclusion, it is suggested that angiotensins may exert their central effects on body fluid and cardiovascular homeostasis mainly via the AT1A receptor subtype.
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PMID:Distribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain. 948 39

Our studies on angiotensin II receptor subtype 1A (AT1A) knockout mice define how endogenous receptors other than AT1A receptors stimulate changes in cytosolic calcium concentration ([Ca2+]i) in cultured aortic vascular smooth muscle cells (VSMCs). Wild-type cells have a 1.7 ratio of AT1A/AT1B receptor mRNA as determined by semiquantitative reverse transcriptase-polymerase chain reaction. Mutant cells express AT1B receptor mRNA but not that for the AT1A receptor. In wild-type cells with AT1A present, Ang II (10(-7) mol/L) produces a characteristic rapid peak increase in [Ca2+]i of 150 to 180 nmol/L, followed by a plateau phase characterized by a sustained 70 to 80 nmol/L increase in [Ca2+]i. An unexpected finding was that the magnitude and time-dependent pattern of [Ca2+]i changes produced by Ang II were similar in cells that lacked AT1A receptors but possessed AT1B receptors. The response in mutant cells indicates effective coupling of an Ang II receptor to one or more second messenger systems. The similarity of response patterns between cells with and without AT1A receptors suggests that non-AT1A receptors are functionally linked to similar signal transduction pathways in mutant cells. The fact that mutant and wild-type cells exhibit similar patterns of calcium mobilization and entry supports the notion that AT1A and non-AT1A receptors share common signal transduction pathways. The AT2 receptor ligands PD-123319 and CGP-42112 do not alter Ang II effects in either VSMC type, suggesting a paucity of AT2 receptors and/or an absence of their linkage to [Ca2+]i pathways. The nonpeptide AT1 receptor blocker losartan antagonizes Ang II-induced [Ca2+]i increases in both cell groups, supporting mediation by native AT1B receptors and effective coupling of this subtype to second messenger systems leading to calcium entry and mobilization. Our results demonstrate that Ang II causes calcium signaling in AT1A-deficient VSMCs that is mediated by an endogenous losartan-sensitive AT1B receptor.
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PMID:Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice. 957 31

This study aimed to investigate the role of endogenous angiotensin II (ANGII) in the upregulation of ANG-II AT1 receptors in adrenal glands during a low-salt intake. To this end male Sprague-Dawley rats were fed a low-salt diet (0.2 mg/g) for 10 days and were treated with the ANGII-AT1 receptor antagonist losartan (40 mg/kg per day) for 2 days, and adrenal mRNA levels for ANGII AT1A and AT1B receptors were determined by RNase protection. The low-salt diet increased AT1A and AT1B receptor mRNA levels by 90% and 220%, respectively. Losartan treatment did not change the basal AT1A mRNA level, but decreased AT1B mRNA by 50%. Treatment of rats on a low-salt diet with losartan did not change the increase of AT1A mRNA but significantly attenuated the increase of AT1B mRNA to 90% of the control value. Stimulation of endogenous ANGII levels by unilateral renal artery clipping for 2 days lowered AT1A mRNA by 25% and increased AT1B mRNA by 30%. Additional treatment with losartan did not affect the decreased AT1A mRNA levels in rats with a unilateral renal artery clip, but significantly attenuated the increase of AT1B mRNA. These findings suggest that sodium deficiency stimulates adrenal AT1A and AT1B receptor mRNA levels primarily via an ANGII-AT1-independent mechanism. The preferential increase of adrenal AT1B mRNA during a low-salt intake could be explained by the elevation of endogenous ANGII levels during sodium deficiency, suggesting that endogenous ANGII acts as an enhancer for adrenal AT1B but not for AT1A receptor gene expression via ANGII-AT1 receptors.
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PMID:Positive feedback regulation of angiotensin II-AT1B receptor gene expression in rat adrenal glands. 964 12

A nonpeptide ligand, L-162,313 (5,7-dimethyl-2-ethyl-3-[[4-[2(n-butyloxycarbonylsulfonamido)-5-is obutyl-3-thienyl]phenyl]methyl]imidazo[4,5,6]pyridine) was characterized on the angiotensin II receptors. This compound displaced [125I][Sar1]angiotensin II from rat angiotensin AT1A, AT1B or AT2 receptor individually expressed in COS-7 cells (Ki = 207 nM, 226 nM and 276 nM, respectively). In monkey kidney cells expressing angiotensin AT1A or AT1B receptors, it stimulated inositol phosphate accumulation, but the maximal response was 34.9 and 23.3%, respectively, of those of angiotensin II. Furthermore, an antagonist effect of L-162.313 was observed in response to angiotensin II. Single-point substitutions in the second and third transmembrane domains of the rat angiotensin AT1A receptor, which impaired the binding of losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1[(1H-tetrazol-5-yl)biphenyl-4 -yl)methyl]imidazole), also affected the binding of L-162,313. Losartan and L-162,313 require some common structural determinants for non-peptide recognition on the angiotensin AT1 receptor. Furthermore, some of these substitutions, which impaired the inositol phosphate accumulation in response to angiotensin II, also impaired the response to L-162,313. Angiotensin II and L-162,313 require common critical residues for angiotensin AT1 receptor activation.
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PMID:Functional interactions of L-162,313 with angiotensin II receptor subtypes and mutants. 965 Aug 56


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