Disease relevance of Tbhpbo

• Using a rat model of cardiac failure, induced by myocardial infarction (MI), we compared the desensitization and resensitization of responses to CGP 12177A with those to isoprenaline and RO 363 in left (LA) and right atria (RA) [1].

High impact information on Tbhpbo

• Denopamine, procaterol, and CGP12177A stimulated oxygen consumption at a concentration of 100 mumol/L [2].
• The presence of beta 3-ARs coupled to lipolysis was demonstrated by the activity of CGP12177A (EC50 = 1.6 mumol/L; intrinsic activity = 62%) [2].
• Overexpression of beta 1-adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for 'putative' beta 4-adrenoceptor pharmacology [3].
• 1. The alpha(1)-adrenoceptor antagonist properties of the beta-adrenoceptor nonconventional partial agonist, CGP 12177A, was investigated in functional assays in rat aorta and in radioligand binding assays in rat cerebral cortical membranes [4].
• BRL37344A and also the other beta(3)-AR agonists, CGP12177A and SR58611A, caused p38 MAPK phosphorylation in dose-dependent manners [5].

Biological context of Tbhpbo

• These data indicate that CGP-12177A is a novel agonist for BAT thermogenesis [6].
• In young rats CGP-12177A increased the number of available BAT mitochondrial GDP binding sites at 20 and 60 min post-injection, but in senescent rats GCP-12177A was unable to increase GDP binding [6].

Anatomical context of Tbhpbo

• 4. CGP12177A had no agonist actions in ileum from either KO or FVB mice [7].
• CL-316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-b enzodioxole-2,2-dicarboxylate] and CGP-12177A [(+/-)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-+ ++benzimidazol-2-one hydrochloride], beta3-adrenoceptor agonists, were more effective in relaxing canine ureter than were dobutamine and procaterol [8].
• OBJECTIVE: To investigate the effects of short term (15 days) cafeteria diet feeding on the expression of beta3-AR in vivo and its association with lipolytic stimulation induced by beta3-AR agonist CGP12177A in isolated white adipocytes [9].

Associations of Tbhpbo with other chemical compounds

• The beta3-AR agonists, CGP-12177A and CL-316243, also suppressed these ureteral contractions, but dobutamine (a beta1-AR agonist) had little relaxing effect [10].
• 3. The p38 MAPK phosphorylations by BRL37344A (10 nM), CGP12177A (100 nM), and SR58611A (10 nM) were not antagonized by beta(1)- and beta(2)-ARs antagonist 1-propranolol (100 nM) but blocked by beta(3)-AR antagonist SR59230A (10 microM), suggesting the phosphorylation was caused via beta(3)-AR [5].
• 6. This study demonstrates enhanced cardiostimulation by CGP 12177A (in the presence of propranolol) in rat ventricular myocytes overexpressing beta(1)-adrenoceptors, mediated by a Gs/cAMP signalling pathway. 'Putative' beta(4)-adrenoceptor pharmacology appears to be mediated by activation of a novel affinity state of the beta(1)-adrenoceptor [3].
• 2. The beta 3-agonists, bucindolol, CGP 12177A and pindolol exhibited the highest binding affinities; BRL 37344, LY 79771, ICI 201651 and SR 58611A presented high potencies in stimulating adenylyl cyclase; bupranolol appeared as the most efficient beta 3-antagonist [11].
• To determine which factors are most important for regulation of ob mRNA expression, we examined the effects of insulin, dexamethasone, a beta3-adrenergic agonist (CGP12177A), 8-bromo-cAMP, 8-bromo-cGMP and 1-methyl-3-isobutylxanthine (MIX) on primary cultured adipocytes [12].

Gene context of Tbhpbo

• At similar high densities of the beta 2-adrenergic receptor, CGP 12177A acted only as a partial agonist [13].
• CGP 12177A originally was developed as a hydrophilic antagonist to detect cell surface beta 1- and beta 2-adrenergic receptors, and subsequently was found to be a partial agonist for the atypical or beta 3-adrenergic receptor [13].
• Pretreatment with CGP 12177A, a beta 3-selective agonist, also reduced beta 3-stimulated adenylyl cyclase activity in transfected 293 cells [14].
• 1. Cardiostimulant effects of the non-conventional partial agonist, CGP 12177A, are mediated by a receptor distinct from the beta3-adrenoceptor and termed the putative beta4-adrenoceptor [1].
• We suggest that CGP 12177A produces its cardiac effects by interacting with a low affinity state of the beta1-adrenoceptor [1].

Analytical, diagnostic and therapeutic context of Tbhpbo

• Frontal displacement affinity chromatography was used to determine the dissociation constants (K(d)) of CGP 12177A (552.6 nM) and (S)-propranolol (84.3 nM) [15].

References