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

1. Agonists and antagonists of kinin B1 and B2 receptors were evaluated in vitro for their effects against angiotensin II (AII)-induced contractile responses in the rabbit aorta and for their binding properties to angiotensin AT1 and AT2 receptors from purified membrane of rat liver and lamb uterus respectively. 2. In aortic rings, the kinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin (BK) (3-100 microM) caused a concentration-dependent decrease in sensitivity and a depression of the maximum response to AII. Des-Arg10-[Leu9]kallidin (KD), des-Arg9-BK, des-Arg10-KD, BK or KD at 3 microM had no effect against AII-induced contractions. 3. Des-Arg9-[Leu8]BK (3 or 100 microM) did not affect contractions of aortic rings to histamine, potassium chloride, endothelin-1, 5-hydroxytryptamine, noradrenaline and the thromboxane A2-mimetic, U46619. 4. Des-Arg9-[Leu8]BK displaced [125I]-Sar1-AII binding to the AT1 subtype in rat liver membranes with a Ki value of 1.1 +/- 0.4 microM. Values of Ki for des-Arg9-BK and KD were 45 +/- 13 microM and 25 +/- 22 microM, respectively. The other kinin derivatives des-Arg10-KD, BK and des-Arg10-[Leu9]KD at concentrations up to 100 microM did not bind to the AT1 receptor. 5. All the kinin derivatives except BK bound to AT2 receptors in lamb uterus membranes. Values of Ki for des-Arg9-[Leu8]BK, des-Arg10-[Leu9]KD, des-Arg9-BK, des-Arg 10-KD and KD were 0.3 +/- 0.1, 0.7 +/- 0.1, 1.2 +/- 0.3, 1.5 +/- 0.3 and 7.0 +/- 1.6 microM, respectively. 6. In conclusion, des-Arg9-[Leu8]BK is an insurmountable antagonist of AII-induced contractions in the rabbit aorta and also binds with a relatively high affinity to AT1 and AT2 receptors in isolated membrane fractions. These additional properties of des-Arg9-[Leu8]BK should be considered when it is used as an antagonist to characterize kinin B1 receptors.
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PMID:The kinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin: an antagonist of the angiotensin AT1 receptor which also binds to the AT2 receptor. 771 6

Angiotensin receptors are present in many tissue types, including adrenal cortex, renal glomeruli, heart, hypothalamus, liver, pancreas, pituitary, platelets, renal tubules, uterus and vascular smooth muscle. Two high-affinity receptor subtypes have been identified by radioligand binding with antagonists: losartan (DuP 753/MK954) identifies AT1 receptors; PD123177 and CGP42112A are markers for AT2 receptors. Angiotensin II may be produced locally in tissues outside the humoral system. For example, it is found in the brain, kidney and heart. Within the brain, the heptapeptide angiotensin(1-7) mimics some effects of angiotensin II, but may be formed directly from angiotensin I. Evidence for non-ACE-mediated angiotensin II production has been reported in the heart. Intravascular angiotensin II receptors are implicated in the central release of vasopressin and other hypophyseal hormones, in increasing sympathetic outflow, in the thirst response and, possibly, in cognitive function; in the inotropic and chronotropic effects of angiotensin II on the heart as well as in growth/hypertrophy; in the control of aldosterone release and in the balance between cortisol and aldosterone secretion; and in modulating sodium, chloride and bicarbonate transport within the kidney. Effects on the reproductive system, liver and pancreas have not been established. The pharmacological effects of angiotensin II antagonists will depend on their distribution characteristics as well as affinity for specific receptor subtypes. At present, however, the physiological role of AT2 receptors has not been defined.
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PMID:Role of angiotensin in the extravascular system. 823 88

Our laboratory has reported previously that a unique binding site specific for the hexapeptide angiotensin (A)II(3-8), now referred to as AIV, is present in a number of tissues including bovine adrenal gland, rabbit and guinea pig heart and guinea pig kidney, liver, lung, uterus and brain. The present results extend previous findings in the guinea pig brain and identify binding sites for AIV in the neocortex, paleocortex, hippocampus, medial habenula, superior and inferior colliculi, caudate putamen, thalamus, dorsal tegmentum, central gray, red nucleus, inferior olivary, oculomotor and hypoglossal nuclei and cerebellum. Binding of [125I]AIV in selected regions was shown to be of high affinity (Kd = 0.60-1.47 nM), saturable (maximal number of binding sites = 181-449 fmol/mg of protein) and specific. This binding site was shown to be distinct from the AT1 and AT2 sites with Ki values > 10(-4) M for DuP 753, CGP42112A and PD123177. Changes at the N-terminal of the peptide, either by removal of the valine or by extension of the peptide, resulted in a large decrease in binding affinity. In contrast, C-terminal extensions resulted in little change in affinity for the binding site. Guanosine 5'-0-(3-thiotriphosphate) was shown to have no effect on binding, suggesting that the guinea pig brain binding site is not G-protein-linked. Potential functions associated with this newly discovered A binding site are discussed.
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PMID:Central angiotensin IV binding sites: distribution and specificity in guinea pig brain. 837 Nov 70

Rat acetyltransferases (ATs) can acetylate the endogenous arylalkylamines tryptamine, 5-hydroxytryptamine (serotonin), and 5-methoxytryptamine, the immediate precursor of melatonin. The same enzymes also acetylate and activate exogenous, carcinogenic arylamines, thereby being immediately responsible for the generation of DNA adducts. Localization of AT transcripts in the pineal gland and in specific cells of the intestine, cerebral cortex, pituitary, and lung identifies cells that may be important to the neurotransmitter and hormonal roles of the tryptamine derivatives. Transcript localization i liver, mammary gland, Zymbal gland, kidney, forestomach, and bladder, as well as intestine and lung, identifies cells that may be at increased carcinogenic risk because they can convert N-hydroxylated arylamines to genotoxic metabolites. Highly specific expression is also observed in the reproductive organs of both the male and female, including the testes, epididymis, uterus, ovary, and fallopian tube. In addition to these diverse organs, which are consistent with possible roles of the enzyme in carcinogen metabolism, neurotransmission, or hormonal regulation, specific cells of the cornea, cilliary process of the eye, olfactory process, adrenal gland, exorbital lacrimal gland, and skin also exhibit highly specific expression of AT mRNAs for which one can only speculate as to their function. In virtually every case, the extent of labeling suggested that AT1 was expressed at levels that were orders of magnitude higher than those of AT2. Qualitative differences in the sites of mRNA of these two enzymes were seen only in the olfactory process, in which AT1 was expressed in both respiratory and olfactory epithelia as well as Bowman's cells, and AT2 was detected only in the latter cells. The available data support the conclusion that the ATs are likely to be involved both in the metabolic activation of exogenous carcinogenic amines as well as the metabolism of endogenous arylalkylamines that play important hormonal and neurotransmitter roles.
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PMID:Histological localization of messenger RNAs for rat acetyltransferases that acetylate serotonin and genotoxic arylamines. 860 96

In contrast to the abundant expression of the AT2 subtype of angiotensin II (AII) receptors during fetal development, AT2 receptor in adult life is expressed in few tissues. We now report studies on the presence and hormonal regulation of AT2 receptor in human pregnant and nonpregnant myometrium obtained from a large study population (n = 50). AT2 receptor subtypes have been characterized using self- and cross-competition curves among [125I]CGP42112A (a selective AT2 ligand), [125I](Sar1,Ile8)AII (a unselective antagonist), the corresponding unlabeled ligands, and several peptidic and nonpeptidic analogs with different affinities for the AT1 and AT2 receptor subtypes. We found that the human nonpregnant uterus expresses almost exclusively the AT2 subtype, and that [125I]CGP42112A is a selective probe to study human AT2 receptor. By using [125I]CGP42112A, we demonstrated that the density of AT2 receptor in human myometrium is dramatically affected by the hormonal milieu. Indeed, in the estrogen-dominant uterus of normal cycling women in the proliferative phase and that of perimenopausal women with anovulatory cycles, the density of binding sites was very high [1565 +/- 246 fmol/mg protein (n = 11) and 2176 +/- 429 (n = 7), respectively]. The concomitant presence of progestogens blunted the estrogen effect [term pregnancy, 61 +/- 12 fmol/mg protein (n = 5); secretive phase of the cycle, 453 +/- 154 (n = 10); combined oral contraceptive, 243 +/- 74 fmol/mg protein (n = 6)]. Very low concentrations of binding sites are also present in the sex steroid-deprived uterus of postmenopausal women (100 +/- 12 fmol/mg protein; n = 8) and the uterus of fertile women chronically treated with GnRH agonists (199 +/- 100 fmol/mg protein; n = 3). Hence, these data confirm the presence of AT2 receptors in human uterus and indicate their regulation by sex steroids.
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PMID:Sex steroid modulation of AT2 receptors in human myometrium. 862 29

Single copies of two closely related acetyltransferase genes were detected in Sprague-Dawley derived rat DNA by Southern blot analysis using gene-specific hybridization probes for the 3' end of the acetyltransferase coding regions. Sequence analysis of the two acetyltransferase genes showed that both had intronless, 870 bp coding regions and coded for 290 amino acid protein sequences that were approximately 85% homologous to one another. The calculated molecular weights were 33.4 and 33.9 kDa and the calculated isoelectric points 4.98 and 5.21 for AT1 and AT2, respectively. The inferred amino acid sequence of both the genes and cDNAs indicated that both rat acetyltransferases have cysteines at positions 44, 68 and 223 which have been conserved in all known vertebrate acetyltransferases. Transcripts for both AT1 and AT2 were detected in brain, colon, esophagus, heart, kidney, liver, lung, mammary gland, dorsal prostate, ventral prostate, salivary gland, seminal vesicles, small intestine, spleen, stomach, testes, urinary bladder and uterus of Sprague-Dawley rats by both Northern blot and RT-PCR analysis. A third gene with >80% sequence homology to codons 118-158 of acetyltransferase was also detected.
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PMID:Genetic analysis of two rat acetyltransferases. 864 Sep 22

The two angiotensin II receptor subtypes, AT1 and AT2, have been reported to be differentially expressed in the myometrial membrane preparations of nulliparous and pregnant sheep, however, their distribution in the sheep reproductive tract has not been reported. The aim of this study is to map the distribution of AT1 and AT2 receptors in the anoestrus reproductive tract of the sheep by quantitative in vitro autoradiography and to investigate if the density and distribution of the receptors change during pregnancy. The AT2 receptor is abundant in a discrete layer in the myometrium of the anoestrus sheep uterus, whilst the AT1 receptor is expressed at lower levels, predominantly in the endometrium. Near-term pregnant uteri, show a marked change in the expression of angiotensin II receptors: the myometrium no longer expresses detectable AT2 receptors but rather, expresses low levels of AT1 receptors. Angiotensin converting enzyme is found in high concentrations in the blood vessels of the pregnant and non-pregnant sheep reproductive system and on the epithelial cells of the fallopian tubes of the non-pregnant sheep. These studies reveal marked reciprocal changes of angiotensin II receptors, with myometrial AT1 receptors increasing during pregnancy, whilst AT2 receptors fall markedly. These changes suggest that angiotensin II may be involved in regulating changes of uterine structure and function during pregnancy by interaction with multiple receptor subtypes.
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PMID:Localization and quantitation of angiotensin AT1 and AT2 receptors in the pregnant and non-pregnant sheep uterus. 870 Oct 38

1. The aim of the present study was to characterize the angiotensin II (AngII) receptor subtypes in the porcine uterus and the variation of receptor densities and renin concentrations during gestation. 2. In myometrium from non-pregnant sows, the AngII receptors were almost exclusively AT2 receptors. During gestation, the AngII receptor density was decreased and the AT1 receptor became predominant in the last part of gestation as a result of a down-regulation of the AT2 receptor. 3. In the endometrium, the AT1 receptor was predominant both in non-pregnant sows and throughout gestation. The AngII receptor density was decreased during gestation as a consequence of down-regulation of the AT1 receptor. 4. The renin concentrations in the myometrium and endometrium of pregnant sows did not differ from those in non-pregnant animals. 5. The finding of enzymatically active renin and high densities of AngII receptors in the porcine uterus is in accordance with a functional renin-angiotensin system (RAS), which may be important for an increased vascular permeability and stimulated angiogenesis in early pregnancy and for contraction of the myometrial smooth muscle cells during parturition. The predominance of AT1 receptors in the endometrium of non-pregnant sows differs from an earlier finding in non-pregnant women, where AT2 receptors were predominant in the endometrium. This is in accordance with earlier studies, indicating species differences in the expression and possibly also the physiological roles of the RAS in reproductive tissues.
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PMID:Angiotensin II receptors and renin in the porcine uterus: myometrial AT2 and endometrial AT1 receptors are down-regulated during gestation. 914 79

Angiotensin II (Ang II) receptors are classified into two subtypes, type 1 (ATF-R) and type 2 (AT2-R) by development of non-peptidic antagonists. Classical Ang II function including vasopressor effect, cardiotropic action and aldosterone production is mainly mediated through AT1-R that present in cardiovascular system, adrenal glands and kidneys. AT1-R is abundantly expressed in whole bodies of fetus and its expression is abruptly decreased after birth, and in the adult AT2-R is expressed in brain nuclei, uterus, adrenal medullary glands and ovary. AT1-R and AT2-R are both G-protein coupled receptors and have 46% similarity in amino acid levels with seventh transmembrane conformation. Signal transduction pathway of AT1-R is mainly CA2+ and activation of protein kinase C, while that of AT2-R is still unknown. Clinical application of AT1-R antagonist started and this causes elevation of plasma Ang II levels, which selectively stimulates AT2-R. Thus, one should realize AT2-R-mediated effect in treatment with AT1-R antagonist. We have shown that AT2-R has anti-AT1-R action, such as inhibitory action against AT1-R-mediated positive chronotropic effect or AT1-R-induced proliferative effect, resulting in the protective effects on Ang II-induced cardiovasucular and renal action. Thus, elucidation of AT2-R function will be important in clinical treatment with AT1-R antagonists.
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PMID:[Pathophysiological function of angiotensin II AT1 and AT2 receptors and clinical application of AT1 antagonists]. 970 75

This review examines the recent progress in the field of angiotensin receptors. Multiplicity of these receptors was demonstrated initially on the basis of pharmacologic differences and then confirmed by expression cloning. AT1 receptors are predominant in the adult. They are widely distributed and mediate all of the known biologic effects of angiotensin II (AngII) through a variety of signal transduction systems, including activation of phospholipases C and A2, inhibition of adenylate cyclase, opening of calcium channels, and activation of tyrosine kinases. AT2 receptors are predominant in the fetus, but also present in adult tissues such as the adrenals, ovaries, uterus, and brain. AngII via these receptors exerts effects often opposed to those mediated by the AT1 receptors. Signal transduction implicates protein tyrosine phosphatase stimulation. AT1 and AT2 receptor expressions are regulated differently, and regulation is also tissue-specific. AT1 and AT2 receptors have been demonstrated in endothelial cells. Activation of AT1 receptors results in production of vasodilatory agents, nitric oxide, and prostacyclin (PGI2), which counteract the direct vasoconstrictor effects of Ang II on the adjacent smooth muscle cells. AT1 receptors on mesangial cells, smooth muscle cells, and fibroblasts are involved in cell growth and fibrosis, the latter being due both to an increase in the synthesis and a decrease in the degradation of the main components of the extracellular matrix. These AT1 receptor-dependent effects are for the most part indirect and mediated by growth factors, cytokines, and other peptides, including endothelin, transforming growth factor-beta1, and platelet-derived growth factor. AngII is metabolized into active fragments by deletion of the terminal amino acids on both ends. AngIII and AngIV are formed by successive deletions of aspartic acid and arginine at the N terminus. AngII (1-7) is obtained by deletion of phenylalanine at the C terminus. AngIII shares the same receptors and exerts the same effects as AngII. AngIV and AngII (1-7) recognize the AT1 and AT2 receptors with a lesser affinity than AngII and, in addition, possess their own receptors that mediate effects often opposed to those of AngII.
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PMID:Angiotensin II receptors. 989 38


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