Effects of quinine on the intracellular calcium level and membrane potential of PC 12 cultures.
The mechanism for the perception of bitterness appears to be quite complicated, even for quinine, which is a model bitter substance, and thus has yet to be completely elucidated. To investigate the possibility of being able to predict the bitterness of quinine solutions, we examined the effects of quinine on intracellular calcium ion concentration ([Ca(2+)]i) and membrane potentials in PC 12 cultures. [Ca(2+)]i and membrane potentials were analysed by fluorescence confocal microscopic imaging using the Ca(2+)-sensitive probe Calcium Green 1/AM and the membrane potential-sensitive probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC(4)(3)). Quinine elicited an increase in the membrane potential along with a concentration-dependent increase in [Ca(2+)]i. These increases were inhibited by extracellular Ca(2+)-free conditions, thapsigargin, which is a Ca(2+)-pump inhibitor, and U73122, which is a phospholipase C inhibitor. The quinine-induced increase in [Ca(2+)]i levels was inhibited by nifedipine, an L-type Ca(2+)-channel blocker, omega-conotoxin, a T-type Ca(2+)-channel blocker, and BMI-40, which is a bitterness-masking substance. These results suggest that responses in PC 12 cultures may be used as a simple model of bitterness perception.
Akiyoshi
Takeshi
T
Department of Clinical Pharmaceutics, Pharmacology, Biochemistry, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Tanaka
Naoko
N
Nakamura
Tomoko
T
Matzno
Sumio
S
Shinozuka
Kazumasa
K
Uchida
Takahiro
T
D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D016716:PC12 Cells; D011803:Quinine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013649:Taste
D000962:Antimalarials; D015220:Calcium Channels; D011803:Quinine; D002118:Calcium