Disease relevance of Brl35135A

• 3. Treatment with BRL 35135 reduced weight gain by 19%, increased brown adipose tissue thermogenic activity 45-fold and reduced plasma insulin by 50% [1].
• No significant changes in body weight occurred during the 10-day treatment with BRL 35135 [2].
• Effect of the beta-adrenoceptor agonist BRL-35135 on development of obesity in suckling Zucker (fa/fa) rats [3].

High impact information on Brl35135A

• BRL 35135 produces a dose-related increase in energy expenditure in rodents and, in genetically obese (ob/ob) mice, a dose of 0.5 mg.kg-1.d-1 has significant antiobesity activity [4].
• After s.c. administration of 3 mg/kg of the selective, rodent specific beta3-AR agonists BRL 35135, CL 316, 243 or ICI 198,157, WT mice exhibited a significant decrease in the extent of movement of radiotracer through the stomach and intestines, indicative of decreased GI motility [5].
• Acute effects of the beta 3-adrenoceptor agonist, BRL 35135, on tissue glucose utilisation [6].
• Higher doses of ZD 7114 and BRL 35135 produced no further increase in HSL activity and, in the case of BRL 35135, provoked symptoms of non-selective beta-adrenoceptor activation [7].
• Food intake was significantly reduced in the BRL 35135-treated-exercise-trained animals, although neither beta 3-agonist nor exercise alone affected it.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

Chemical compound and disease context of Brl35135A

• The results suggest that BRL 35135 improves glucose tolerance by an increase in insulin sensitivity that is independent of body weight [2].

Biological context of Brl35135A

• In conclusion, pre-obese Zucker fa/fa rats are responsive to BRL 35135 treatment: acute administration of this drug was able to improve impaired thermogenesis and to correct temporarily other abnormalities of early emergence in BAT [8].
• 7 In conclusion, BRL 35135 produced airways, potassium and glucose responses which were antagonised by nadolol, whereas the lipolysis response was not [9].
• Chronic treatment with BRL 35135 potentiates the action of insulin on lipid metabolism [10].
• Beta-adrenoceptor subtypes mediating the metabolic effects of BRL 35135 in man [11].
• BRL 35135 treatment increased expression levels of beta3-AR mRNA in both genotypes [12].

Anatomical context of Brl35135A

• This study was undertaken to determine whether acute injection of the beta-adrenoceptor BRL 35135, which is known to activate thermogenesis, could correct the earliest detectable metabolic abnormalities that characterize brown (BAT) and white (WAT) adipose tissues of pre-obese Zucker rats [8].
• EC50 and relative intrinsic activity values were obtained for isoprenaline, fenoterol, salbutamol, prenalterol and three new beta-adrenoceptor agonists, BRL 28410, BRL 35113 and BRL 35135 on rat white adipocyte lipolysis, rat atrial rate and tension, rat uterus tension and guinea-pig tracheal tension [13].
• In lean rats, skeletal muscle UCP-3 mRNA was increased 2.3 fold by BRL 35135 whereas UCP-2 was reduced by 2.2 fold [12].
• The effect of an atypical beta-adrenoceptor agonist, BRL-35135 on leukotriene B4-induced-guinea pig eosinophil chemotaxis was studied [14].

Associations of Brl35135A with other chemical compounds

• Differential regulation of uncoupling proteins by chronic treatments with beta 3-adrenergic agonist BRL 35135 and metformin in obese fa/fa Zucker rats [15].
• In this study, we compared the chronic effects of antihyperglycemic doses of the TZD rosiglitazone, the beta3-adrenoceptor agonist BRL-35135, and the PPARalpha agonist Wy-14,643 on the mRNA expression of adipocytokines in WAT of db/db mice [16].

Gene context of Brl35135A

• In WAT BRL 35135 increased UCP-2 and UCP-3 expression 2-3 fold in both lean and fa/fa rats [12].
• In comparison, Wy-14,643 reduced adiponectin transcript levels by 31% (P = 0.015) while BRL-35135 increased RELMalpha mRNA expression by 245% (P < 0.001) without effect on the other transcripts [16].
• Potentiation of the anti-obesity effect of the selective beta 3-adrenoceptor agonist BRL 35135 in obese Zucker rats by exercise [1].
• 1 The purpose of the study was to assess the bronchorelaxant effects of the beta3-adrenoceptor agonist BRL 35135 in normal human airways [9].
• Acute injection of beta-adrenoceptor agonist BRL 35135 corrects both impaired uncoupling protein and lipoprotein lipase gene expression but not hypercapacity of lipogenesis in brown adipose tissue of suckling fa/fa rats [8].

Analytical, diagnostic and therapeutic context of Brl35135A

• Fa/fa and fa/fa littermates were given oral administration of BRL-35135 from 8 to 16 days of age [3].

References