Dual effect of 1.4-dihydropyridines on Ca2+ inflow into rat pancreatic islet cells.
The present study aimed at comparing the effects of nifedipine, a dihydropyridine "Ca2+ antagonist", and of BAY K 8644, a dihydropyridine "Ca2+ agonist", on the short term (5 min) 45Ca uptake and the cytosolic Ca2+ concentration of rat pancreatic islet cells incubated in the presence of physiological concentrations of glucose. Nanomolar concentrations of nifedipine increased the short term 45Ca uptake while micromolar concentrations decreased it. Cd2+, an inorganic Ca2+ channel blocker, reduced the stimulatory effect of nifedipine. Low concentrations of BAY K 8644 stimulated 45Ca uptake whereas high concentrations decreased it. In contrast, verapamil, a phenylalkylamine type calcium antagonist, only provoked a dose-dependent reduction in 45Ca uptake. Lastly, low concentrations of both nifedipine and BAY K 8644 raised the fluorescence intensity of fura 2 loaded islet cells. These findings indicate that nifedipine and BAY K 8644 may exhibit agonistic and antagonistic actions on B-cell voltage-dependent Ca2+ channels. This dualistic behaviour is markedly concentration-dependent and appears to be inherent to the 1,4-dihydropyridine compounds.
Plasman
P O
PO
Laboratory of Pharmacology, Faculty of Medicine, Brussels Free University, Belgium.
Herchuelz
A
A
Lebrun
P
P
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D003470:Culture Media; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005453:Fluorescence; D016257:Fura-2; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
D002132:Calcium Radioisotopes; D003470:Culture Media; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D005947:Glucose; D002118:Calcium; D016257:Fura-2