Comparison of binding affinities and calcium current inhibitory effects of a 1,4-dihydropyridine derivative (PN 200-110) in vascular smooth muscle.
The binding of (+) (3H) PN 200-110 to high and low affinity sites in mammalian portal vein smooth muscle membranes was characterized. Binding affinities were 0.09 and 30 nM for the high and low affinity sites, respectively, and binding site densities were 45 and 400 fmoles/mg of protein for the respective sites. (+) PN 200-110 blocked both fast and slow calcium currents in isolated cells from portal vein smooth muscle. The blockade of slow calcium current was voltage-dependent as PN 200-110 bound with higher affinity to inactivated slow calcium channels (IC50 = 0.03 nM) than to resting channels (IC50 = 0.15 nM). The blockade of fast calcium current was voltage-independent (IC50 = 45 nM). The IC50 values found from electrophysiological experiments for the binding to inactivated slow and fast calcium channels are similar to the Kd values determined by radioligand binding.
Dacquet
C
C
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, I.B.C.N. du C.N.R.S., Université Bordeaux II, France.
Pacaud
P
P
Loirand
G
G
Mironneau
C
C
Mironneau
J
J
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D006736:Horses; D017275:Isradipine; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D013237:Stereoisomerism
D010069:Oxadiazoles; D009529:Nicardipine; D002118:Calcium; D017275:Isradipine