High affinity binding of the calcium channel blocker, (+)-[methyl-3H]PN200-110(3HPN) in rat brain.
PN200-110 is a recently introduced 1,4-dihydropyridine which has been demonstrated to be a potent calcium channel blocker. 3HPN has been shown to bind in a specific saturable manner to P2 fractions obtained from brain homogenates from male Sprague-Dawley rats. 3HPN binding was found to be temperature-dependent. Specific 3HPN binding was maximal at 25 degrees C; binding decreased at 2 degrees C and 37 degrees C. The KD calculated from Scatchard analysis was 0.0943 +/- 0.0038 nM while the Bmax was found to be 109.1 +/- 2.3 fmol/mg protein. A concentration dependent inhibition of 3HPN binding by various cations was determined and found to be as follows: ZN2+ greater than La3+ greater than Rh3+, Al3+ greater than Co2+, Ni2+, Mn2+ greater than Ca2+, Mg2+ greater than Ba2+ greater than Sr2+. These results provide evidence for the existence of central high affinity dihydropyridine receptor sites in rat brain.
Magill
S B
SB
Department of Physiology, University of North Dakota, School of Medicine, Grand Forks 58202.
Stone
J S
JS
Parmar
S S
SS
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017275:Isradipine; D008297:Male; D009543:Nifedipine / Q000493:pharmacokinetics; D010069:Oxadiazoles / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D009543:Nifedipine; D017275:Isradipine