Disease relevance of NSC707473

• The combination of prazosin and cyanopindolol resulted in an abolishment of MDMA-induced hyperthermia [1].
• 2. Heart rate was dose-dependently increased by CGP 12177 and cyanopindolol by maximally 150 and 100 beats min(-1), yielding pED50 values of 8.0 and 7.3, respectively (pED50, -log10 of the dose in mol kg(-1) body weight i.v. causing the half-maximum effect), but not affected by the selective beta3-adrenoceptor agonist CL 316243 (pED50 > 6.0) [2].
• The 8-OH-DPAT-induced hypothermia is not affected by cyanopindolol or compound 21009 [3].
• Tachycardia to CGP12177 and cyanopindolol was not blocked by propranolol (3 x 10(-7) M) in atria from either group [4].
• Ischemia was verified by decreased regional blood flow (radioactive microspheres) and loss of systolic regional wall motion in the ischemic zone. beta-Adrenergic receptor density assessed by 125I-labeled cyanopindolol binding in a crude membrane fraction tended to decrease but was not significantly different [5].

High impact information on NSC707473

• We have recently reported that the highly potent beta-adrenergic affinity label [125I]bromoacetylamino cyanopindolol ([125I]BAM-CYP) irreversibly blocks the turkey erythrocyte beta-adrenoceptor binding site by combining with a receptor-associated non-protein component [6].
• The neuropeptide somatostatin potentiates beta-adrenergic receptor-mediated cAMP formation in astrocytes derived from neonatal rat cortex but does not affect cAMP levels by itself. beta-Adrenergic receptors in these cells can be specifically labeled with the high affinity antagonist [125I] cyanopindolol ([125I]CYP) [7].
• Beta-receptors were measured in longitudinal sections of ligated rat sciatic nerve by autoradiographic localization of 125I-labeled cyanopindolol binding sites [8].
• METHODS: Employing enriched nuclear preparations, we assayed the specific presence of betaAR by measuring 125I-cyanopindolol (CYP) binding, Western blotting, confocal microscopy and functional assays [9].
• The response to 5-HT was reversed by the 5-HT1 receptor antagonists cyanopindolol and pindolol, but not the 5-HT2 receptor antagonist ketanserin [10].

Chemical compound and disease context of NSC707473

• Both the hypothermias studied are blocked or reversed by pindolol, cyanopindolol and compound 21-009, but not by atenolol [3].

Biological context of NSC707473

• Castration resulted in decreased catecholamine-induced as well as forskolin-induced lipolysis. beta-adrenoceptor number, examined by a whole cell cyanopindolol binding assay, was also diminished to a similar extent [11].
• 8. CGP 12177 0.01 and 0.1 mumol kg-1 and cyanopindolol 1 mumol kg-1 elicited an increase in diastolic blood pressure [12].
• [3H]5-CT binding was inhibited by cyanopindolol with an IC50 of 0.87 +/- 0.30 nM, suggesting the expression of the 5-HT1B receptor in these neurons [13].
• EPO levels did not elevate, even after bloodletting to load anemia, and the EPO circadian rhythm was irregular in 6-OHDA-treated rats. beta-adrenergic receptors measured using 125I-cyanopindolol (CYP) significantly decreased from day 7 to day 28, and reached normal values after day 35 [14].

Anatomical context of NSC707473

• Beta-adrenergic receptors were characterized in human fat cell membranes using 125I-labeled cyanopindolol (125I-labeled CYP) and highly selective beta 1-antagonists [15].
• Atypical responses of rat ileum to pindolol, cyanopindolol and iodocyanopindolol [16].
• 3 In WKY, CGP 12177 and cyanopindolol produced an endothelium and nitric oxide (NO)-independent relaxation [17].
• 4. Neither (-)-CGP 12177 nor cyanopindolol caused stimulant effects in papillary muscles at concentrations between 0.2 nM and 20 microM [18].
• 5 Radioligand binding studies, using iodinated cyanopindolol, were performed to determine beta(2)-adrenoceptor density in cell membranes after pretreatment (24 h) of cells with either salbutamol (10(-6) M) or terbutaline (10(-6) M) [19].

Associations of NSC707473 with other chemical compounds

• Ketanserin, spiperone, ritanserin, LY53857, 1-napthylpiperazine, 1-(3-chlorophenyl)-piperazine, rauwolscine, ICS 205-930, cyanopindolol and sumatriptan all blocked 5-HT-induced contractions in guinea pig trachea [20].
• Studies with the beta3 receptor antagonist cyanopindolol and the beta3 receptor agonist BRL37344 revealed that beta adrenergic regulation of spontaneous contractions and responses to nerve stimulation were mediated primarily by the beta3 adrenoreceptor [21].
• Neither did the 5-HT3-receptor antagonist MDL 72222 or the selective 5-HT1 binding ligand cyanopindolol [22].
• The 5-HT1A, 5-HT1B and beta-adrenergic receptor antagonists pindolol and cyanopindolol (6 mg/kg SC) did not affect punished responding either, nor did the 5-HT1D receptor partial agonist and alpha 2 adrenergic receptor antagonist yohimbine (2.5 mg/kg SC) or the histamine H1 receptor antagonist mepyramine (1 mg/kg SC) [23].
• This selectivity was considerably greater than that observed for other beta-adrenoceptor ligands including propranolol (5-HT1A/5-HT1B ratio = 2), oxpenolol (3.5) and cyanopindolol (8.7) [24].

Gene context of NSC707473

• These data provide definitive evidence that the receptor mediating tachycardia to CGP12177 and to cyanopindolol in atria from the transgenic beta3 receptor knockout mice is neither the beta1, beta2, nor beta3 adrenergic receptor [4].
• (+/-)Cyanopindolol (3 and 8 mg/kg), an antagonist at 5-HT1A and 5-HT1B receptors, had no effect whereas 8-hydroxy-2-di-n-propylamino)tetralin (30-300 micrograms/kg), an agonist at 5-HT1A receptors, significantly attenuated the hypophagia [25].
• No specific binding was detected with [125I] cyanopindolol in either fresh cortical biopsies or post-mortem tissues, suggesting that the apparent absence of 5-HT1B receptor sites reported earlier was not related to long post-mortem delays [26].
• The 5-HT1A/B/D antagonist, cyanopindolol, which is inactive at 5-HT7 receptors, did not antagonize the actions of 8-OH-DPAT [27].
• However, the number of beta 2-adrenoceptor binding sites as assessed by radioligand binding with 125I-labelled cyanopindolol was not changed [28].

Analytical, diagnostic and therapeutic context of NSC707473

• This rapid, sensitive, simple radioreceptor assay (RRA) for l-propranolol and its active metabolites in unextracted samples requires 5 microL of sample, a beta-adrenergic antagonist, 125-l-labeled (-)cyanopindolol (125ICYP), and turkey erythrocyte membrane receptors (Kd = 40 pmol/L) [29].
• Site-directed mutagenesis of the rat beta1-adrenoceptor. Involvement of Tyr356 (7.43) in (+/-)cyanopindolol but not (+/-)[125Iodo]cyanopindolol binding [30].
• Total tissue content of beta-receptors was measured in frozen sections of skeletal muscle biopsies incubated with 125I-labeled cyanopindolol in the presence and absence of 10(-5) M L-propranolol [31].
• 1. Binding sites in guinea pig myocardial tissue labelled by (-)-[125I] cyanopindolol (CYP) were investigated using differential centrifugation and autoradiographic techniques [32].

References