更新于：2024-11-01

α1A-AR x GR

更新于：2024-11-01

基本信息

关联

项与 α1A-AR x GR 相关的药物

Mometasone furoate/Oxymetazoline Hydrochloride

莫米松糠酸酯/盐酸羟甲唑啉

靶点

GR x α1A-AR

作用机制

GR激动剂 [+1]

在研机构-

原研机构

Merck & Co., Inc.

在研适应症-

非在研适应症

季节性过敏性鼻炎

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 α1A-AR x GR 相关的临床结果

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100 项与 α1A-AR x GR 相关的转化医学

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0 项与 α1A-AR x GR 相关的专利（医药）

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项与 α1A-AR x GR 相关的文献（医药）

2021-02-01·Bulletin of Experimental Biology and Medicine4区 · 医学

Influence of Social Isolation Stress on Age-Related Changes in Functional Activity and Expression of Receptors of Endogenous Vasoconstrictors in Rat Aorta

4区 · 医学

Article

作者: Kryzhanovskii, S A ; Tsorin, I B ; Sukhanova, I F ; Kozhevnikova, L M ; Vititnova, M B

Social isolation stress was modeled by long-term isolation of 12-month-old rats in individual cages over 28 weeks. It was found that sensitization of blood vessels to the vasoconstrictor action of serotonin due to overexpression of 5HT2A-type receptor genes, as well as an imbalance in the expression level of endothelin ETA- and ETB-receptors (55 and 153%, respectively) are the early signs of vascular aging. A significant contribution to the development of age-related changes in the contractile properties of blood vessels is made by the stress component, which is manifested at the level of glucocorticoid-dependent mechanisms of regulation of gene expression. The decrease in the expression of glucocorticoid receptors caused by isolation stress leads to a decrease in the expression of the genes responsible for the synthesis of V1A-R and ATII-R and to the development of vascular hyporeactivity to the vasoconstrictor action of ATII and AVP. In the aorta of stressed rats, the α1-AR mRNA level increases by 3 times. At the same time, stress did not affect the dynamics of age-related changes in the expression of genes encoding 5HT2A-R and ETA/ETB-R.

2017-02-01·Journal of Dairy Science1区 · 农林科学

Variable liver fat concentration as a proxy for body fat mobilization postpartum has minor effects on insulin-induced changes in hepatic gene expression related to energy metabolism in dairy cows

1区 · 农林科学

Article

作者: Röntgen, M ; Börner, S ; Kautzsch, U ; Erdmann, S ; Schäff, C T ; Kuhla, B ; Weber, C ; Bruckmaier, R M ; Hammon, H M

The liver plays a central role in adaptation for energy requirements around calving, and changes in the effects of insulin on hepatic energy metabolism contribute to metabolic adaptation in dairy cows. Hepatic insulin effects may depend on body fat mobilization. The objective of this study was to investigate the effects of insulin on the hepatic gene expression of enzymes involved in energy metabolism and factors related to nutrition partitioning in cows with high and low total liver fat concentration (LFC) after calving. Holstein cows were retrospectively grouped according to their LFC after calving as a proxy for body fat mobilization. Cows were classified as low (LLFC; LFC <24% fat/dry matter; n = 9) and high (HLFC; LFC >24.4% fat/dry matter; n = 10) fat-mobilizing after calving. Euglycemic-hyperinsulinemic clamps [6 mU/(kg × min) of insulin for 6 h] were performed in wk 5 antepartum (ap) and wk 3 postpartum (pp). Before and at the end of the euglycemic-hyperinsulinemic clamps, liver biopsies were taken to measure the mRNA abundance of enzymes involved in carbohydrate and lipid metabolism, expression related to the somatotropic axis, and adrenergic and glucocorticoid receptors. The mRNA abundance of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK; PCK1), acyl-CoA-dehydrogenase very long chain (ACADVL), and hydroxyl-methyl-glutaryl-CoA-synthase 1 increased, but the mRNA abundance of solute carrier family 2 (SLC2A2 and SLC2A4), growth hormone receptor 1A (GHR1A), insulin-like growth factor 1 (IGF1), sterol regulatory element binding factor 1, adrenoceptor α 1A, and glucocorticoid receptor decreased from ap to pp. Insulin treatment was associated with decreased PCK1, mitochondrial PEPCK, glucose-6-phosphatase, propionyl-CoA-carboxylase α, carnitine-palmitoyl-transferase 1A, ACADVL, and insulin receptor mRNA, but increased IGF1 and SLC2A4 mRNA ap and pp and GHR1A mRNA pp. The mRNA abundance of SLC2A4 was greater, and the mRNA abundance of GHR1A and IGF1 tended to be lower in LLFC than in HLFC. Administration of insulin, albeit at a supraphysiological dose, was associated with inhibition of gene expression related to glucose production and β-oxidation, but we observed variable effects in the degree of insulin depression of individual genes. Insulin status is important for regulation of nutrient partitioning, but different LFC pp had very little influence on changes in hepatic gene expression following administration of insulin.

2014-10-01·Journal of Dairy Science1区 · 农林科学

Effects of colostrum versus formula feeding on hepatic glucocorticoid and α1- and β2-adrenergic receptors in neonatal calves and their effect on glucose and lipid metabolism

1区 · 农林科学

Article

作者: Steinhoff-Wagner, J ; Bruckmaier, R M ; Hammon, H M ; Schäff, C T ; Kanitz, E ; Rohrbeck, D ; Sauerwein, H

Neonatal energy metabolism in calves has to adapt to extrauterine life and depends on colostrum feeding. The adrenergic and glucocorticoid systems are involved in postnatal maturation of pathways related to energy metabolism and calves show elevated plasma concentrations of cortisol and catecholamines during perinatal life. We tested the hypothesis that hepatic glucocorticoid receptors (GR) and α₁- and β₂-adrenergic receptors (AR) in neonatal calves are involved in adaptation of postnatal energy metabolism and that respective binding capacities depend on colostrum feeding. Calves were fed colostrum (CF; n=7) or a milk-based formula (FF; n=7) with similar nutrient content up to d 4 of life. Blood samples were taken daily before feeding and 2h after feeding on d 4 of life to measure metabolites and hormones related to energy metabolism in blood plasma. Liver tissue was obtained 2 h after feeding on d 4 to measure hepatic fat content and binding capacity of AR and GR. Maximal binding capacity and binding affinity were calculated by saturation binding assays using [(3)H]-prazosin and [(3)H]-CGP-12177 for determination of α₁- and β₂-AR and [(3)H]-dexamethasone for determination of GR in liver. Additional liver samples were taken to measure mRNA abundance of AR and GR, and of key enzymes related to hepatic glucose and lipid metabolism. Plasma concentrations of albumin, triacylglycerides, insulin-like growth factor I, leptin, and thyroid hormones changed until d 4 and all these variables except leptin and thyroid hormones responded to feed intake on d 4. Diet effects were determined for albumin, insulin-like growth factor I, leptin, and thyroid hormones. Binding capacity for GR was greater and for α₁-AR tended to be greater in CF than in FF calves. Binding affinities were in the same range for each receptor type. Gene expression of α₁-AR (ADRA1) tended to be lower in CF than FF calves. Binding capacity of GR was related to parameters of glucose and lipid metabolism, whereas β₂-AR binding capacity was negatively associated with glucose metabolism. In conclusion, our results indicate a dependence of GR and α₁-AR on milk feeding immediately after birth and point to an involvement of hepatic GR and AR in postnatal adaptation of glucose and lipid metabolism in calves.