Nisoldipine blocks the increase of intracellular free calcium-ion concentration associated with elevated sodium-lithium countertransport activity in erythrocytes in patients with NIDDM.
To understand the mechanism by which elevated sodium-lithium countertransport activity (SLC) associates with increased intracellular free calcium-ion concentration ([Ca2+]i), we investigated the relationship between SLC and the effects of the extracellular Ca2+ concentration ([Ca2+]o) and a Ca2(+)-channel blocker, nisoldipine, on [Ca2+]i in erythrocytes from 48 patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). There was a significant correlation between SLC and [Ca2+]i. Nisoldipine in the incubation medium significantly decreased [Ca2+]i, and there was a significant positive correlation between SLC and the degree of [Ca2+]i decrease. When the [Ca2+]o was elevated, [Ca2+]i was significantly increased, but nisoldipine almost completely suppressed this increase of [Ca2+]i. There was a significant positive correlation between SLC and the degree of the suppression. These data suggest that elevated SLC correlates with increased [Ca2+]i, and that the increased [Ca2i]i might be due to the increased Ca2+ influx through a dihydropyridine-sensitive Ca2+ pathway.
Fujita
J
J
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Sakyo-ku, Japan.
Tsuda
K
K
Obayashi
H
H
Fukui
I
I
Ishida
H
H
Seino
Y
Y
D000328:Adult; D017920:Antiporters / Q000097:blood*; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D004912:Erythrocytes / Q000737:chemistry* / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008094:Lithium / Q000097:blood; D008297:Male; D008875:Middle Aged; D015737:Nisoldipine / Q000494:pharmacology*; D012964:Sodium / Q000097:blood
D017920:Antiporters; D002121:Calcium Channel Blockers; C045885:sodium-lithium countertransporter; D015737:Nisoldipine; D008094:Lithium; D012964:Sodium; D002118:Calcium