Effects of Ca2+ channel agonist-antagonist enantiomers of dihydropyridine 202791 on insulin release, 45Ca uptake and electrical activity in isolated pancreatic islets.
This is the first study using the selective agonist/antagonist stereoisomers of dihydropyridine 202791 to investigate stimulus-secretion coupling in pancreatic islet cells. We studied effects of the (+)(Ca2+ channel agonist) and (-)(Ca2+ channel antagonist) forms of the dihydropyridine, on 45calcium net uptake, insulin secretion, and membrane potential measured in rodent islets. The antagonist partially inhibited glucose-induced insulin secretion and Ca2+ uptake; however, the potassium-induced Ca2+ uptake was completely inhibited. The antagonist did not completely block glucose-evoked spike activity. Addition of the agonist enhanced insulin release and Ca2+ uptake in the presence of 5.6 mM-glucose, but did not increase insulin release or Ca2+ uptake in 16.7 mM-glucose. In the presence of tetraethylammonium (TEA), (+)202791 increased and (-)202791 decreased the duration of glucose-induced action potentials. The results again confirm the presence of a dihydropyridine-sensitive Ca2+ channel in pancreatic B-cells. In addition these data suggest that in these cells there is activation of a dihydropyridine-insensitive Ca2+ entry in the presence of glucose.
Boschero
A C
AC
Laboratory of Cell Biology and Genetics, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Carroll
P B
PB
De Souza
C
C
Atwater
I
I
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007328:Insulin; C045796:SAN 202791; D009543:Nifedipine; D002118:Calcium