Disease relevance of CGP 20712A

• 2. Sinoatrial tachycardia, evoked by (-)-adrenaline was resistant to blockade by beta(2)-selective ICI 118,551 (50 nM) but antagonized by beta(1)-selective CGP 20712A (300 nM) [1].
• In left atria obtained from mice injected with 150 microg/kg i.p. pertussis toxin which abolished carbachol-evoked cardiode-pression, the positive inotropic effects of (-)-adrenaline were antagonised by CGP 20712A [2].

High impact information on CGP 20712A

• When 300 nmol/L CGP 20712A was present as the sole antagonist, only a marginal shift of the concentration-response curve for (-)-epinephrine was usually observed, indicating that beta 1AR were not mediating the effect of these low concentrations of (-)-epinephrine [3].
• Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta 1 AR (CGP 20712A) and beta 2 AR (ICI 118,551) [3].
• The beta-adrenergic antagonists CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2-selective) blocked in a dose-dependent fashion the ability of isoproterenol to effect receptor mRNA levels [4].
• In contrast, beta2AR stimulation by zinterol or isoproterenol plus a selective beta1-adrenergic receptor (beta1AR) antagonist CGP 20712A failed to enhance the contractility in TG4 myocytes, and more surprisingly, beta2AR stimulation was also ineffective in increasing contractility in WT myocytes [5].
• In the presence of CGP 20712A (beta 1-receptor blocker), a 100-fold higher concentration of zinterol increased the amplitude but prolonged the duration of the twitch in adult myocytes [6].

Chemical compound and disease context of CGP 20712A

• Pretreatment with pertussis toxin abolished the action of CGP 20712A on basal cAMP [7].

Biological context of CGP 20712A

• At equimolar concentrations, the beta 1-selective antagonist CGP-20712A provided a greater degree of inhibition of catecholamine-stimulated lipolysis than the beta 2-selective antagonist ICI-118,551 [8].
• The selective beta 1 adrenoceptor antagonist CGP20712A (100 nmol.litre-1) displaced about 30% and 50% of the total atrioventricular node binding sites in diabetic and control hearts, respectively [9].
• Isoproterenol stimulation of I(sc) and cAMP was inhibited by ICI-118551 (IC50 = 6 microM for I(sc)) but not by CGP-20712A (1 microM) in primary cultures, and similar results were found in native epithelium [10].
• Furthermore, EPI-induced up-regulation of alpha-subunit expression can be blocked by the preferential beta(2)-adrenoceptor antagonist ICI 118,551 but not by the preferential beta(1)-adrenoceptor antagonist CGP 20712A [11].
• In the presence of CGP 20712A (0.1 microM) alone, isoprenaline (1 microM) still induced a significant increase in contractility but the action potential profile was only slightly affected [12].

Anatomical context of CGP 20712A

• Positive inotropic responses were established to (-)-isoprenaline, RO363 (beta 1-selective), procaterol (beta 2-selective) and dopexamine in the absence or presence of the antagonist CGP 20712A (beta 1-selective) or ICI 118,551 (beta 2-selective) in electrically driven human right atrial appendage strips [13].
• In rat adipocyte membranes, displacement of [125I]ICYP by CGP 20712A and ICI 118,551 was biphasic, indicating high and low affinity sites; displacement profiles differed markedly between lumbar and parametrial depots, the former having a preponderance of beta 1-like receptors and the latter a preponderance of beta 2-like receptors [14].
• 1. The nature of the beta-adrenoceptor(s) mediating adenylyl cyclase activation in rat adipocyte ghosts by (-)-isoprenaline and the lipolytically selective beta-adrenoceptor agonist, BRL 37344, was investigated by use of the beta 1-selective antagonist, CGP 20712A [15].
• 4. The beta-AR agonist RO363 relaxed the ileum (pEC50=6.18) and was blocked by CGP20712A [16].
• In plantaris muscle, monophasic competition curves were observed when binding experiments were performed using CGP20712A (50 pM to 0.5 mM), a beta 1-adrenoceptor selective antagonist, or ICI 118,551 (50 pM to 20 microM), a beta 2-adrenoceptor selective antagonist, to compete for ICYP binding [17].

Associations of CGP 20712A with other chemical compounds

• This acidification, which was also observed in myocytes that were preloaded with the Ca2+ chelator BAPTA and superfused with nominally Ca(2+)-free solution, was blocked by propranolol as well as by the specific beta 1-antagonist CGP 20712 A but not by the beta 2-antagonist ICI 118,551 [18].
• Among 11 beta antagonists tested, only ICI118551 and CGP20712A, previously classified as, respectively, beta 1 and beta 2 selective, inhibit this effect [19].
• Inhibition of agonist-stimulated cyclic AMP production and competition binding experiments indicated that the beta 1-selective antagonists CGP 20712A and ICI 89,406 were much more potent than the beta 2-selective antagonist ICI 118,551 [20].
• The apoptosis induced by the non-specific beta-AR agonist isoproterenol was largely blocked by the beta(1)-selective antagonist CGP 20712A, but not by the beta(2)-selective antagonist ICI 118551 [21].
• Pharmacological tests showed that the beta(2)-adrenoceptor antagonist, ICI118,551, but not the beta(1)-adrenoceptor antagonist, CGP20712A, blocked the NE-induced IPSC facilitation, suggesting that the beta(2)-adrenoceptors on cerebellar interneurons, basket cells (BCs), mediate the noradrenergic facilitation of GABAergic transmission [22].

Gene context of CGP 20712A

• Studies with CGP20712A or the beta 2AR-selective antagonist ICI118,551 indicated that this residual response was predominantly beta 2AR in character [23].
• The pD(2) and pA(2) values of (-)-isoprenaline and CGP 20712A, respectively, were not different in left atria and right atria from mdx and C57 mice [24].
• Iso stimulation at doses that reduced BNP mRNA expression increased TUNEL positive nuclei, an effect blocked by the beta1-antagonist CGP [25].
• 3. Direct measurement of tissue radioactivity also showed that specific I-CYP binding was competitively inhibited in the presence of the beta-adrenoceptor antagonists (-)-propranolol (non-selective), CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2-selective) [26].
• 3. Increases of ventricular force by (-)-adrenaline and (-)-noradrenaline were not blocked by ICI 118,551 but antagonized by CGP 20712A [1].

Analytical, diagnostic and therapeutic context of CGP 20712A

• We characterized beta-adrenoceptors in rat sinoatrial node (SA) and stellate ganglia by incubating consecutive tissue sections with [125I]iodocyanopindolol, with or without the beta 1-selective (CGP 20712A) or the beta 2-selective (ICI 118,551) antagonists, followed by quantitative autoradiography [27].

References