Characterization of a novel, hydrophilic dihydropyridine, NKY-722, as a Ca2+ antagonist in bovine cultured adrenal chromaffin cells.
1. To characterize NKY-722, a novel hydrophilic dihydropyridine derivative, as a Ca2+ antagonist, we examined its effects on 45Ca2+ influx, intracellular free Ca2+ concentrations [( Ca2+]i), and release of noradrenaline and adrenaline in bovine cultured adrenal chromaffin cells. 2. NKY-722 had little effect on basal 45Ca2+ influx into the resting cells, but inhibited high K+ (35.9 mM)-evoked 45Ca2+ influx in a concentration-dependent manner with an IC50 value of 5.2 nM. 3. NKY-722 inhibited high K(+)-evoked increases in [Ca2+]i in a concentration-dependent manner without effect on the resting [Ca2+]i. 4. NKY-722 had little effect on basal release of noradrenaline and adrenaline but inhibited high K(+)-evoked release of noradrenaline and adrenaline in a concentration-dependent manner with IC50 values of 5.0 nM and 4.8 nM, respectively. 5. Nicardipine, a prototype of NKY-722, also inhibited high K(+)-evoked 45Ca2+ influx and release of noradrenaline and adrenaline in a concentration-dependent manner: the IC50 value for high K(+)-evoked 45Ca2+ influx was 51 nM, and the values for high K(+)-evoked release of noradrenaline and adrenaline were 52 nM and 50 nM, respectively. 6. These results show that NKY-722 is a hydrophilic Ca2+ antagonist ten times more potent than nicardipine.
Ohue
T
T
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Lee
K
K
Koshimura
K
K
Miwa
S
S
D000311:Adrenal Glands / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011188:Potassium / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002395:Catecholamines; D004095:Dihydropyridines; C058351:NKY 722; D011188:Potassium; D002118:Calcium