Participation of intracellular sites in the action of Ca2+ channel blockers.
The action of phenylalkylamine Ca2+ channel blockers D890 and D888 on Ca2+ uptake and neurotransmitter amino acid release were studied. D890, the quaternary derivative of D600, did not inhibit veratrine-induced 45Ca2+ uptake or the release of neurotransmitter amino acids from rat cerebrocortical synaptosomes, except at high concentrations (200 microM) when it was probably acting extracellularly in a non-specific manner. This contrasted with the more potent (10-50 microM) inhibitory actions of D600 and D888, and may be due to the inability of D890 to cross the synaptic plasma membrane. (-)D888 was shown to cross cell membranes and accumulate in the intracellular compartment of cerebrocortical slices and synaptosomes, where it was associated predominantly with the soluble cytoplasmic fraction.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000378:metabolism; D005711:Gallopamil / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000031:analogs & derivatives* / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology
D000596:Amino Acids; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D005711:Gallopamil; C041386:D 890; C043184:4-desmethoxyverapamil; D014700:Verapamil; D014702:Veratrine; D011188:Potassium