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Title: | (-)[3H]amlodipine binding to rat cardiac membranes. | Austin Authors: | Nayler, W G;Gu, X H | Affiliation: | Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia | Issue Date: | 1-Apr-1991 | Publication information: | Journal of Cardiovascular Pharmacology; 17(4): 587-92 | Abstract: | Amlodipine is a newly developed long-acting dihydropyridine-based calcium antagonist. To characterize the binding properties of this compound, saturation binding studies were undertaken, using (-)[3H]amlodipine and rat cardiac membrane fragments. (-)[3H]Amlodipine bound to a single population of high-affinity binding sites with a KD of 1.68 +/- 0.12 nM, a Bmax of 0.34 +/- 0.08 pmol/mg protein, and a Hill coefficient approaching unity. Binding required up to 5 h to reach asymptote, and was pH- and temperature-sensitive. The specific binding was totally inhibited by (-) amlodipine and (-) D600 (IC50 values of 9.20 +/- 5.56 and 6.58 +/- 6.57 nM, respectively) and only partially inhibited by (+) PN 200-110, (-) Bay K 8644, (+) D600, and d-cis diltiazem (IC50 values of 60 +/- 10, 160 +/- 20, 250 +/- 40, and 200 +/- 30 nM, respectively). These results indicate that in addition to its ability to bind to the dihydropyridine and benzothiazepine recognition sites in rat cardiac membrane fragments, (-)[3H]amlodipine also binds strongly to the recognition sites for the phenylalkylamine-based calcium antagonists. The results also show that the inhibition of (-)[3H]amlodipine binding by D600 is stereospecific with (-) greater than (+)D600. Dissociation of bound (-)[3H]amlodipine was slowed under acidotic (pH 6.0) and accelerated under alkalotic (pH 10.0) conditions. | Gov't Doc #: | 1711625 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/10274 | Journal: | Journal of Cardiovascular Pharmacology | URL: | https://pubmed.ncbi.nlm.nih.gov/1711625 | Type: | Journal Article | Subjects: | Amlodipine Animals Female Gallopamil.pharmacology Hydrogen-Ion Concentration In Vitro Techniques Isradipine Kinetics Membranes.metabolism Myocardium.metabolism Nifedipine.analogs & derivatives.metabolism Oxadiazoles.pharmacology Rats Rats, Inbred Strains Stereoisomerism Temperature |
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