Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (AII) receptor binding assays were performed in rat adipocytes from three separate anatomic depots. Fat cells were isolated by collagenase digestion, and plasma membranes were prepared from the epididymal, mesenteric, and retroperitoneal fat depots of male Sprague-Dawley rats at 100 days of age. Binding of 125I-labeled [Sar1,Ile8]AII was rapid, saturable, and specific in membranes from all depots, identifying a receptor with a similar affinity of approximately 1 nM. Site-associated differences in receptor number were observed, with epididymal and mesenteric fat cell membranes exhibiting significantly more receptors than retroperitoneal fat cells when binding was expressed per unit of membrane protein. When corrected for cell volume, the number of receptors per cell ranked epididymal > retroperitoneal > mesenteric. Inhibitory constants for the peptide agonists AII and AIII and the peptide antagonist [Sar1,Ala8]AII indicated similar affinities in all three depots. Because the receptor has been classified pharmacologically into two subtypes, the AT1 selective antagonist losartan, and the AT2 selective antagonist PD 123,319 were used to classify the adipocyte receptor, indicating an AT1 subtype with an affinity for losartan in the mesenteric and retroperitoneal adipocytes that was significantly greater than the epididymal. Similar studies were performed in adipocyte membranes obtained from human omental and subcutaneous adipose tissue, revealing the presence of an AII receptor in both depots with an affinity of approximately 10 nM for losartan. These data indicate site-specific differences in AII receptor number in fat cell membranes from rats and the existence of human adipocyte AII receptors, suggesting that the adipocyte is significant for the peripheral metabolism of components of the renin-angiotensin system.
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PMID:Distribution of angiotensin II receptors in rat and human adipocytes. 798 62

Angiotensin had a dual action on the epididymal half of rat vas deferens. It potentiated electrical stimulated contraction and exerted a direct contractile effect on the muscle. The potentiation of electrically stimulated response may be mediated by presynaptic facilitation of neurotransmitter release. Muscular contractile response to angiotensin is concentration dependent. Angiotensin II was found to be much more potent than angiotensin III, and the order of potencies was angiotensin II > angiotensin I > angiotensin III. The presence of a mixture of protease inhibitors (10 microM chymostatin, 50 microM bacitracin, 10 microM leupeptin and 10 microM pepstatin) did not alter the contractile activity of angiotensin II. In contrast, angiotensin I (10 nM)-induced contraction was significantly reduced in the presence of ACE inhibitor SQ 20881 (500 nM). The angiotensin II induced contraction was not reduced by CGP 42112, a specific AT2 receptor antagonist, but was significantly inhibited by losartan, a specific AT1 receptor antagonist. Losartan shifted the dose-response curve of angiotensin II to the right with a pA2 value of 8.68. In addition, p-aminophenylalanine6 angiotensin II, which is proposed as an AT2 receptor agonist, did not induce contraction. It is concluded that the AT1 receptor predominantly mediates angiotensin-induced contraction in epididymal rat vas deferens.
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PMID:Characterization of contractile response to angiotensin in epididymal rat vas deferens. 858 70

Characterization and regulation of angiotensin II (AII) receptor binding sites was performed in rat membrane preparations from nonadipose (liver, lung) and adipose (interscapular (ISBAT) and periaortic (PA) brown adipose tissue; epididymal (EF) and retroperitoneal (RPF) white adipose tissue). In membrane preparations from brown and white adipose sources, [125I]AII saturation binding revealed a single, high affinity (Kd range of 0.3 -0.6 nM) binding site with a modest AII receptor density (Bmax range of 17-120 fmol/mg protein) comparable to rat lung (130 fmol/mg protein). White adipose tissue contained a greater number of AII receptor sites than brown adipose tissue. Competition displacement studies demonstrated the AT1 receptor is the only angiotensin receptor subtype localized in adipose tissue, with the rank order for competition of [125I]AII binding in all adipose tissues examined AIII > AII > losartan > angiotensin I (AI) > PD123319. The AT2 specific receptor antagonist, PD123319, was ineffective at displacing [125I]AII binding in all adipose tissues examined. Since components of the renin-angiotensin system are regulated in adipose tissue, we determined if the AII receptor is also regulated in the obese state. AII receptor binding characteristics were determined in liver, lung, ISBAT and EF membrane preparations from adult Zucker obese (fa/fa) and lean (Fa/?) rats. AII receptor density was decreased in liver from obese rats. In contrast, the affinity for [125I]AII binding was not altered in tissues from obese rats. In a separate group of obese and lean rats, regulation of the AII receptor by phenobarbital (PB) was examined. Administration of PB restored AII receptor density in liver from obese rats to levels obtained in lean rats. In summary, these results demonstrate the presence of AT1 receptor sites in brown and white adipose tissue. Moreover, AII receptor density is decreased in tissues from obese rats, with restoration of receptor density by administration of PB. Future studies will determine if PB regulates the AT1 receptor at the level of gene expression.
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PMID:Characterization and regulation of angiotensin II receptors in rat adipose tissue. Angiotensin receptors in adipose tissue. 872 84

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.
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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.
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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.
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PMID:Differential gene expression of angiotensin II receptor subtypes in the epididymides of mature and immature rats. 944 37

Adipose tissue is recognized as a pivotal organ in the development of insulin resistance. This study seeks to determine the effect of angiotensin receptor blockade (ARB) on insulin resistance of adipocytes in culture and in a rat model of type 2 diabetes. Treatment of Otsuka Long-Evans Tokushima Fatty rats with the ARB L158809 for six months significantly lowered fasting plasma glucose, cholesterol and triglyceride levels but led to higher plasma adiponectin levels. Insulin resistance, measured by an intraperitoneal glucose tolerance test, of the treated rats was significantly improved along with an increase in the number of small differentiated adipocytes; however, epididymal fat mass decreased. Treatment significantly lowered lipid peroxidation and MCP-1 expression while increasing adiponectin production by the adipose tissue. ARB treatment significantly improved insulin sensitivity and markedly suppressed AT2-induced oxidative stress, PAI-1 and MCP-1 levels and NF-kappaB activation of adipocytes in culture. Treatment increased adiponectin and PPARgamma expression along with intracellular triglyceride levels reflecting differentiation of the cultured adipocytes. Our study suggests that ARB treatment improves insulin resistance by modification of adipose tissue thereby blunting the development of diabetes.
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PMID:Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue. 1879 17