Dihydropyridines binding site

Schleifer K-J. Stereoselective characterization of the 1,4-dihydropyridine binding site at L-type calcium channels in the resting state and the opened/inactivated state. J Med Chem 1999 42 2204-11. 

Antkiewicz-Michaluk, L., Michaluk, J., Romanska, I., Vetulani, J. Cortical dihydropyridine binding sites and a behavioral syndrome in morphine-abstinent rats, Eur. J. Pharmacol. 1990, 180, 129-135. 

Ramkumar, V. and El-Fakahany, E.E. Prolonged morphine treatment increases rat brain dihydropyridine binding sites possible involvement in development of morphine dependence, Eur. J. Pharmacol. 1988, 146, 73-83. 

Halothane has a mUd depressive effect on cardiac performance (4). In human ventricular myocardium, halothane interacted with L-type calcium channels by interfering with the dihydropyridine binding site this may, at least in part, explain its negative inotropic effect (5). 

Nimodipine 288 has been labelled with C in order to study the density of the L-type calcium channels and the dihydropyridine binding sites (equation 115) with the PET technique . ... 

A. Schwartz, Motif iii s5 of 1-type calcium channels is involved in the dihydropyridine binding site, a combined radioligand binding and electrophysiological study, /. Biol. Chem. 1997, 272(5), 2629-33. 

Jarrahian, A. and Hillard, C.J. (1997) Arachidonylethanolamide (anandamide) binds with low affinity to dihydropyridine binding sites in brain membranes. Prostaglandins Leukot. Essent. Fatty Acids, 57 551. ... 

Ferry, D.R., Russell, M.A., and Cullen, M.H. (1992) P-glycoprotein possesses a 1,4-dihydropyridine-selective drug acceptor site which is alloserically coupled to a vinca-alkaloid-selective binding site. Biochem Biophys Res Commun, 188, 110-445. 

Several 1,4-dihydropyridine calcium channel blockers have been tritiated and used to investigate binding of this class of drugs. The majority of studies utilized [3H]nitrendipine [26, 87-115], but [3H]nimodipine [ 115-123], [3H]nifedipine [124] and [3H]PN 200-110 [97,106,125,126] have also been employed in some studies. Drug binding has been shown to be specific, saturable, rapid and reversible. Scatchard plots of the specific binding at equilibrium are linear, consistent with mass action behaviour. The apparent dissociation constant (A d) and the number of binding sites (Bmax) may be determined from the Scatchard plot. 

The dihydropyridine- (DHP)-sensitive calcium channel purified from skeletal muscle is composed of five subunits al9 a2, P, y, and 8 (9-12). The cty subunit (molecular weight Mr 170 kD) forms a functional voltage-gated calcium channel (9, 13-15) and contains the binding sites for the three classes of calcium channel modulators 1,4-dihydropyridines (16), phenylal-kylamines, and benzothiazepines (17). The primary structure of the ax subunit was first elucidated from skeletal muscle (18) highly homologous sequences have since been cloned from cardiac muscle (13, 19, 20) and brain (21), aorta (22), and lung (23) tissue. 

No. Binding sites for drugs of the dihydropyridine class are separate from those of other calcium channel blockers. 

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