Interaction between perchlorate and nifedipine on insulin secretion from mouse pancreatic islets.
In order to elucidate the mechanisms responsible for the stimulatory effect of perchlorate (ClO4-) on insulin secretion, we have investigated the interaction between this chaotropic anion and the organic calcium antagonist nifedipine. This drug, known as a blocker of L-type calcium channels, was chosen as a tool to test the idea that ClO4- acts on insulin secretion by stimulating the gating of voltage-controlled Ca2+ channels. ClO4- amplified the stimulatory effect of D-glucose on insulin release from perfused pancreas (first and second phases) as well as from isolated islets incubated in static incubations for 60 min. This indicates that ClO4- amplifies physiologically regulated insulin secretion. Nifedipine reduced D-glucose-induced (20 mM) insulin release in a dose-dependent manner with half-maximum effect at about 0.8 microM and apparent maximum effect at 5 microM nifedipine. In the presence of 20 mM D-glucose, the inhibitory effects of 0.5, 1 or 5 microM nifedipine were only slightly, if at all, counteracted by perchlorate. When 12 mM ClO4- and 20 mM D-glucose were combined, calculation of the specific effect of ClO4- revealed that nifedipine produced almost maximum inhibition already at 0.05 microM. Thus, the perchlorate-induced amplification of D-glucose-stimulated insulin release shows higher sensitivity to nifedipine than the D-glucose-effect as such. This supports the hypothesis that perchlorate primarily affects the voltage-sensitive L-type calcium channel in the beta-cell.
Department of Histology and Cell Biology, University of Umeå, Sweden.
G
G
Larsson-Nyrén
J
J
Sehlin
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009543:Nifedipine / Q000008:administration & dosage*; D010472:Perchlorates / Q000008:administration & dosage*; D010477:Perfusion; D017670:Sodium Compounds
D015220:Calcium Channels; D007328:Insulin; D010472:Perchlorates; D017670:Sodium Compounds; C031068:sodium perchlorate; D009543:Nifedipine; D005947:Glucose