Displacement of [3H]phencyclidine binding to Torpedo electric organ membrane by calcium channel antagonists.

Rerentty, Quirion and Pert [I] reported that certain calcium antagonists displace ~3~]pkeu~~c~id~~e ~~3~]P~P~ ~~~d~~g in rat brain. They found fkat verapamif, and its methxy derivative, D-600), were potent displacers of @I]PCP binding with X; values of 1.4 and 1.7 #VI respectively. In contrast, two calcium antagonists of the 1,4-dihydropyridine series, nifedipine and nitrendipine, were very weak displacers af [3H]PCP binding, with Ki values >iOOpM. Eldefrawi ef al. 121 reoorted the nresence of a high-affinity binding site fo; iwjpcp in crayfish abdom&I mu& c&l = 13.5 nM), and this [-‘fi]PCP binding was also displaced by calcium antagonists. The rcsD values for displacement of (?i]PCP binding to crayfish muscle by these antagonists, as determined by extrapolation from the fignre presented by Eidefrawi er nl [Z], were: verapamil = 0.06 &f, (c)-D-600 = 0.2 ,UM, (-)-D-s00 = 0‘4 J&f, and &Eedipine -= IO FM_ Hence, in crayfish muscle, as in rat brain, nifedlpirie was considerably weaker than verapamif in displacement of [3HjPCP binding, although in mayfisk muscle all of the antago~~ts were mm potent than in rat brain, In our laboratory, we have been studying the mechanism of action of calcium channel antagonists [J]. As part of our studies, we examined the influence of calcium antagonists on [‘H]PCP binding to microsacs isolated from the electric organ of Torpedo caiifornica, which have been shown to be a rich source for the specific binding of E3HJP&P [4]. Consistent with the findings in rat brain and crayfish muscle, we find that vrrapamil potently displaced [%I]PCP binding to Torpedo microsacs. However, in contrast to these other tissues, in Tnrpiida microsacs, some calcium charm& antagonist of the 1~4-dihvdro~vrid~ne series, as well as the d~phenylmet~ylalkyi~m~n~ series, were more potent than verapamil as antagonists of @?@“CP binding. CaCl, abo displaced ]%-TfPCP binding to Torn&o microsacs. Tkese s&has @g&t that the c&urn channel antagonists may interact with the ionic channel associated with the nicotinic acetylcholine receptor in Torpedo electric organ membranes. A preliminary report of these findings has been published previously [S].