The imidazoline derivative calmidazolium inhibits voltage-gated Ca(2+)-channels and insulin release but has no effect on the phospholipase C system in insulin producing RINm5F-cells.
The present study shows that the calmodulin antagonist calmidazolium inhibited influx of Ca2+ through voltage-gated Ca(2+)-channels in clonal insulin producing RINm5F-cells. The mechanism of inhibition may involve both Ca(2+)-calmodulin-dependent protein kinases and direct binding of calmidazolium to the Ca(2+)-channel. Calmidazolium did not affect uptake of Ca2+ into intracellular Ca(2+)-pools, inositol 1,4,5-trisphosphate (InsP3) formation or action on intracellular Ca(2+)-pools. The calmodulin inhibitor also did not affect glucose utilization or oxidation in RINm5F-cells, speaking against an unspecific toxic effect of the compound. KCl-and ATP-stimulated insulin release from RINm5F-cells was attenuated by calmidazolium, whereas basal hormone secretion was unaffected.
Kindmark
H
H
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Köhler
M
M
Gerwins
P
P
Larsson
O
O
Khan
A
A
Wahl
M A
MA
Berggren
P O
PO
D000818:Animals; D002118:Calcium / Q000032:analysis; D002121:Calcium Channel Blockers; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002999:Clone Cells; D005947:Glucose / Q000032:analysis; D007093:Imidazoles / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D002121:Calcium Channel Blockers; D002147:Calmodulin; D007093:Imidazoles; D007328:Insulin; C031938:calmidazolium; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D005947:Glucose; D002118:Calcium