Effects of Ca2+ channel antagonists and their isomers on glibenclamide-sensitive K+ currents in follicle-enclosed Xenopus oocytes.
Several Ca2+ channel antagonists were shown to inhibit glibenclamide-sensitive K+ currents in follicle-enclosed Xenopus oocytes. We have investigated the stereoselectivity of the effects of Ca2+ channel antagonists on the glibenclamide-sensitive K+ currents induced by Y-26763 (a K+ channel opener) in follicle-enclosed Xenopus oocytes. (-)-Bepridil and (+)-bepridil similarly suppressed Y-26763-induced K+ currents with IC50 values of 7.8 microM and 7.4 microM, respectively. The Ca2+ channel antagonists, (-)- and (+/-)-verapamil, and inactive (+)-verapamil suppressed Y-26763-induced K+ currents to similar extents and their IC50 values were 63.1 microM and 55.0 microM, respectively. The Ca2+ channel antagonist, SD-3211 and its less potent (-)-isomer, SD-3212, suppressed Y-26763-induced K+ currents with similar IC50 values of 10.7 microM and 8.9 microM, respectively. Of all the Ca2+ channel antagonists tested, only diltiazem exhibited stereoselectivity. The rank order of potencies (IC50 in microM) of four isomers of diltiazem to block Y-26763-induced K+ currents was (+)-trans (4.2) > (-)-trans (13.3) > (-)-cis (35.8) > (+)-cis (75.9), which was, however, opposite to that of their potencies as Ca2+ channel antagonists. These results indicate that blockade by Ca2+ channel antagonists of glibenclamide-sensitive K+ currents in follicle-enclosed Xenopus oocytes is not mediated by Ca2+ channel antagonism.
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
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Sakuta
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Okamoto
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007536:Isomerism; D000442:Octanols / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014982:Xenopus laevis
D000959:Antihypertensive Agents; D001578:Benzopyrans; D002121:Calcium Channel Blockers; D000442:Octanols; D015221:Potassium Channels; D013779:Tetrodotoxin; C074338:Y 26763; D005905:Glyburide