Academic Journal
MC225, a Novel Probe for P-glycoprotein PET imaging at the Blood-Brain Barrier: in vitro cardivascular safety evaluation
| العنوان: | MC225, a Novel Probe for P-glycoprotein PET imaging at the Blood-Brain Barrier: in vitro cardivascular safety evaluation |
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| المؤلفون: | Fusi F, Durante M, Gorelli B, Perrone MG, Colabufo NA, Saponara S. |
| المساهمون: | Fusi, F, Durante, M, Gorelli, B, Perrone, Mg, Colabufo, Na, Saponara, S. |
| سنة النشر: | 2017 |
| المجموعة: | Università degli Studi di Bari Aldo Moro: CINECA IRIS |
| مصطلحات موضوعية: | aorta ring, Ca(V)1.2 channel current, Langendorff-perfused heart, PET tracer, P-glycoprotein KeyWords Plus: RESISTANCE-REVERTING AGENTS, PERFUSED RAT-HEART, 3,5-DIBENZOYL-4-(3-PHENOXYPHENYL)-1,4-DIHYDRO-2,6-DIMETHYLPYRIDINE DP7, PARKINSONS-DISEASE, TRANSPORTERS, PHARMACOLOGY, CONDUCTION, ECG |
| الوصف: | The P-glycoprotein (P-gp) substrate MC225, at concentrations <= 10 nM, is a valuable radiotracer for positron emission tomography imaging of P-gp function in rats and mice. The aim of this study was to evaluate its potential toxic hazard toward the cardiovascular system through an in-depth analysis of its effects on rat aorta rings, on Ca(V)1.2 channel current (I-Ca1.2) of A7r5 cells and on Langendorff-perfused rat heart. In aortic rings, MC225 relaxed phenylephrine-induced contraction in a concentration-dependent and endothelium-independent manner, with an IC50 value of about 1 mu M. At concentrations >= 3 mu M, it antagonized the response to cumulative concentrations of K+. MC225, 1 and 10 mM, inhibited ICa1.2 by 15% and 31%, respectively, without affecting either current activation or inactivation kinetics. In Langendorff-perfused rat hearts, only 10 mM MC225 significantly decreased left ventricular pressure and increased coronary perfusion pressure while reducing heart rate and prolonging the cardiac cycle length as well as the atrioventricular conduction time (PQ interval) on the electrocardiogram. Lower concentrations of the drug were ineffective. These findings demonstrate that MC225-induced cardiovascular effects took place at concentrations that are at least 2 orders of magnitude higher than those allowing in vivo measurement of P-gp function. Therefore, MC225 represents a promising positron emission tomography tool for in vivo straightforward P-gp quantification. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/28877068; info:eu-repo/semantics/altIdentifier/wos/WOS:000419203400008; volume:70; issue:6; firstpage:405; lastpage:410; numberofpages:6; journal:JOURNAL OF CARDIOVASCULAR PHARMACOLOGY; http://hdl.handle.net/11586/206092; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85040777800 |
| DOI: | 10.1097/FJC.0000000000000536 |
| الاتاحة: | http://hdl.handle.net/11586/206092 https://doi.org/10.1097/FJC.0000000000000536 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.D94DB1F0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1097/FJC.0000000000000536 |
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