Pharmacological characterization of the voltage-dependent calcium channel of pancreatic B-cell.
Pharmacological characteristics of the voltage-dependent calcium channel (VDCC) of the pancreatic B-cell were studied using omega-conotoxin (omega CgTX) and dihydropyridine (DHP) calcium channel blockers. High glucose and potassium (K+) depolarization were employed as the stimulant of insulin release. omega CgTX (greater than 50 nM), a blocker of neural, but not muscular, Ca2+ channels, partially blocked (27%) the second, but not the first, phase of glucose-induced insulin release without a significant effect on K+ depolarization-induced insulin release. The DHP Ca2+ channel blocker nifedipine inhibited both phases of glucose-induced insulin release (ED50 = 200 nM) and completely abolished both phases of response at 10 microM. In contrast, the DHP Ca2+ channel blocker only partially suppressed (75% at 10 microM) K+ depolarization-induced insulin release with an ED50 of 100 nM. We conclude that pancreatic B-cell possesses at least two classes of VDCCs; one is DHP sensitive, and the other DHP insensitive. Partial suppression of the second phase of glucose-induced insulin release by a high concentration of omega CgTX may be due to its toxic effect on the secretory machinery other than VDCC.
Komatsu
M
M
Department of Geriatrics, Endocrinology, and Metabolism, Shinshu University School of Medicine, Nagano-ken, Japan.
Yokokawa
N
N
Takeda
T
T
Nagasawa
Y
Y
Aizawa
T
T
Yamada
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D007328:Insulin; D008978:Mollusk Venoms; D011189:Potassium Chloride; C038806:1,4-dihydropyridine; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D005947:Glucose; D011188:Potassium