Dihydropiridines mechanism of action in striatal isolated nerve endings: comparison with omega-agatoxin IVA.
The relative contribution of Ca2+ and Na+ channels to the mechanism underlying the action of the dihydropiridines (DHPs), nimodipine, nitrendipine and nifedipine was investigated in rat striatum synaptosomes. The rise in internal Ca2+ (Ca(i), as determined with fura-2) induced by high K+ was unchanged by the DHPs, which like tetrodotoxin (TTX) inhibited both the rise in internal Na+ (Na(i), as determined with the Na+ selective indicator dye, SBFI) and the rise in Ca(i) induced by veratridine. Nimodipine and nitrendipine were much more potent than nifedipine. Oppositely to TTX and to the DHPs, the P/Q type Ca2+ channel blocker, omega-agatoxin IVA did not inhibit the rise in Ca(i) induced by veratridine, but inhibited the rise in Ca(i) induced by high K+. Veratridine-evoked release of dopamine, GABA, Glu, and Asp (detected by HPLC) was inhibited by nimodipine, nitrendipine, and TTX, while high K+-evoked release was unchanged by the DHPs or TTX. It is concluded that the reduction in presynaptic Na+ channel permeability might contribute to the cerebral effects of DHPs.
Galindo
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CA
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México.
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D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009411:Nerve Endings / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020867:omega-Agatoxin IVA / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D020867:omega-Agatoxin IVA; C038806:1,4-dihydropyridine