Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study receptors for angiotensin II, polyclonal rabbit anti-peptide antisera were prepared against the peptide QDDCPKAGRHC corresponding to amino acids 15-24 of the rat AT1A and AT1B receptors. Western analysis of rat tissues showed a major band of approximately 43 kDa. The antisera immunoprecipitated AT1-receptor protein produced in vitro. Immunohistochemical analysis of rat tissues showed intense staining of arterial and arteriolar smooth muscle. Other tissues that contained AT1-receptor protein included hepatocytes, the zona glomerulosa of the adrenal gland, and the smooth muscle of the bronchus, gut, ureter, and epididymis. In the kidney, intense staining was observed in all small arteries and arterioles. Both afferent and efferent arterioles contain approximately equal intensities of immunoreactive AT1 protein. The inner stripe of the outer medulla has a moderate level of receptors within thick ascending limb epithelium. Proximal tubular epithelium also expresses receptor protein. Glomerular immunoreactive AT1 protein is found within mesangial cells and varies in intensity among different rat strains. Lewis and Wistar rats demonstrated moderate glomerular staining, whereas the CD and Sprague-Dawley strains showed lesser levels of reactivity. The fact that glomerular mesangial cells are the primary locus of angiotensin II action within the glomerulus.
 ...
PMID:Immunohistochemical localization of rat angiotensin II AT1 receptor. 768 19

Evaluation of angiotensin II (AII) receptor binding often necessitates freezing of the tissue of interest prior to assay of radioligand binding. This study evaluated the effects of freezing of various rat tissues at different rates on 125I-sarcosine1, isoleucine8 angiotensin II (125I-SI AII) binding to AII receptor subtypes. Slow freezing in a -20 degrees C compartment significantly reduced 125I-SI AII binding to AT1 receptors in the adrenal (51%), epididymis (34%), and liver (22%). Binding of 12tI-SI AII to the AT1 receptor in the brain was not significantly reduced. In the adrenal, both the Bmax and affinity of AT1 receptors were decreased by freezing. But in the epididymis, only the affinity of AT1 receptors was decreased. Binding of 125I-SI AII to AT2 receptors in the adrenal, epididymis, and brain was also not significantly reduced by freezing. Further evaluation of the mechanism of the reduction in 125I-SI AII binding to AT1 receptors in the adrenal indicated that both the receptor density and affinity for 125I-SI AII were decreased by freezing. Rapid freezing in a dry-ice bath caused even greater reductions in 125I-SI AII binding to AT1 receptors in the adrenal. Snap freezing in liquid nitrogen decreased 125I-SI AII binding in adrenals to a similar extent as did slow freezing. These results suggest that studies of AII receptors subtypes that involve freezing of the tissues underestimate the density and affinity of the AT1 receptor subtype.
 ...
PMID:Influence of tissue freezing on the binding of 125I-sarcosine1, isoleucine8 angiotensin II to angiotensin II receptor subtypes in the rat. 776 20

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.
 ...
PMID:Histological localization of messenger RNAs for rat acetyltransferases that acetylate serotonin and genotoxic arylamines. 860 96

Previous studies from our laboratory have provided evidence for the existence of a local renin-angiotensin system in the rat epididymis. Evidence has also accumulated, indicating that locally formed angiotensin II from the rat epididymis may play a paracrine and/or autocrine role in regulating epididymal electrolyte and fluid transport. In the present study, specific anti-peptide antibodies against the second extracellular loops of angiotensin II type I (AT1) and type II (AT2) receptors were used to localize immunocytochemically these receptors in the rat cauda epididymides of three developmental stages, namely, immature (2-week), early mature (6-week) and fully mature (10-week). The immunostaining intensity for AT1 receptors was found to be stronger than that for AT2 receptors throughout rat epididymides of all stages. However, the immunostaining for both AT1 and AT2 receptors observed in the fully mature rat epididymis was much more intense than that observed in the epididymides of the two younger stages. While the immunostaining for both AT1 and AT2 receptors in the younger rat epididymides appeared to be distributed in both basal and apical regions, the immunostaining in the fully mature epididymis was predominantly localized in the basal region. The present finding of the differential patterns of angiotensin II receptor immunoreactivity in three different stages of the rat epididymis may reflect the fine tuning of rat epididymal function by angiotensin II, acting as a paracrine or autocrine agent, during the course of development.
 ...
PMID:Angiotensin II receptors: localization of type I and type II in rat epididymides of different developmental stages. 914 62

Previous work from our laboratory has provided evidence for the presence of a tissue renin-angiotensin system in the rat epididymis. In the current investigation, the regional localization of angiotensin II receptors, type I (AT1) and type II (AT2) was studied immunocytochemically using specific anti-peptide antibodies against the second extracellular loops of AT1 and AT2 receptors, and pharmacologically using specific receptor antagonists in conjunction with the short-circuit current technique. The immunocytochemical results showed that AT1 and AT2 immunoreactivities were predominantly localized in the basal region of the epididymal epithelium. Electrophysiological studies using the short-circuit current technique demonstrated a stimulatory effect of basolaterally applied angiotensin II on the epididymal electrogenic ion transport. This effect was inhibitable by the addition of AT1 antagonist, losartan but not by AT2 antagonist, PD123177, indicating a functional role of AT1 in epididymal electrolyte transport. The present finding suggests that angiotensin II receptors may play an important role in the regulation of epididymal function.
 ...
PMID:Angiotensin II receptors, AT1 and AT2 in the rat epididymis. Immunocytochemical and electrophysiological studies. 920 76

Previous studies have suggested that epididymal and sperm functions are subject to control by a local renin-angiotensin II system (RAS) in the rat epididymis. Type-1 angiotensin II receptor, AT1 and type-2 receptor, AT2 were localized in epididymal epithelium, indicating that RAS may act in a paracrine or autocrine fashion to regulate fluid secretion, probably through the basally placed membrane-bound AT1 protein as revealed by immunocytochemical and electrophysiological studies. In the present work, the expression of the angiotensin II receptor subtypes in the rat epididymis was showed by western blot analysis and reverse-transcription polymerase chain reaction (RT-PCR) using specific primers for the angiotensin II receptor subtypes. Western blot analysis showed the expression of AT1 receptor in the rat epididymis. Results from RT-PCR, using specific primers based on the corresponding angiotensin II receptor subtype genes for AT1a, AT1b and AT2 , demonstrated the differential expression of mRNAs from these receptor subtypes in the epididymides of mature and immature rats. Both the genes for AT1a and AT1b, but not that for AT2, are predominantly expressed in the epididymides of mature rat. In contrast, only AT1a and AT2 were highly expressed in the epididymides of immature rat. These results suggest that the expression of type-1 and type-2 angiotensin II receptor subtypes are developmentally regulated. Type-1 subtype may play a role in regulation of electrolyte and fluid transport in mature rat whereas type-2 subtype may be important in growth and development in the immature rat.
 ...
PMID:Differential gene expression of angiotensin II receptor subtypes in the epididymides of mature and immature rats. 944 37

Evidence for the existence of an intrinsic angiotensin system based on locally formed angiotensinogen as a precursor for angiotensin production has been demonstrated in the rat epididymis. The data strongly support the presence of an epididymal renin-angiotensin system (RAS) which may be important for epididymal and sperm functions. In the present study, the effects of castration and testicular hormonal replacement on the expression of RAS components from the rat epididymis are investigated at the gene and protein levels. Results from northern blot and western blot analyses consistently showed that the expression of angiotensinogen mRNA and protein was apparently abolished by castration whereas their expression was completely restored to control levels when the castrated rats were hormonally replaced with either testosterone alone or with combined testosterone and estradiol. Northern blot did not detect any signal for angiotensinogen mRNA while western blot could detect a weak signal for angiotensinogen protein when the castrated rats were replaced with estradiol alone. Renin could be detected neither in control, castrated nor hormonally replaced rats. Moreover, the expression of angiotensin II receptor, type I (AT1) was almost abolished by castration as demonstrated by northern blot and reverse transcription-polymerase chain reaction. These data indicate that the expression of RAS by the rat epididymis at the levels of its precursor angiotensinogen and its receptor AT1, is subject to the regulation of testicular hormones and its expression appears to be predominantly testosterone-dependent.
 ...
PMID:Testicular hormonal regulation of the renin-angiotensin system in the rat epididymis. 1075 67

Angiotensin II (AngII) is the biologically active peptide of the renin-angiotensin system (RAS). Tissue- based, local RAS has been identified in the prostate, testis, epididymis and coagulating glands. Experimental and clinical studies have consistently shown that myocardial infarction (MI) is associated with activation of the systemic RAS with increased concentration of angiotensin peptides in the blood and changes in expression of angiotensin receptors (AT). Changes in angiotensin receptors in the renal and cardiovascular system after MI are well recognized, but the effects of MI influence on changes in other tissue like the prostate gland are unknown. In the present study, we investigated the effect of myocardial infarction on angiotensin receptor protein and mRNA expression in the rat prostate gland. MI model was established in Wistar rats by ligating the left coronary artery (modified Selye method). The levels of AT1a-b and AT2 receptor mRNAs and proteins were measured in the rat prostate. Our study demonstrates tissue-specific changes in AT1a-b and AT2 receptor expression after myocardial infarction. The results show that MI has a strong influence on the expression of angiotensin receptor type AT1 in the prostate at the protein and mRNA level.
 ...
PMID:Influence of myocardial infarction on changes in the expression of angiotensin type 1 receptor in the rat prostate. 2203 31