Neuronal Ca2+ channel blocking action of an antihypertensive drug, cilnidipine, in IMR-32 human neuroblastoma cells.
Although the anti-sympathetic mechanisms of the antihypertensive drug cilnidipine have been analyzed in neuronal cells derived from rodents, there is little information regarding the effects of cilnidipine in human neuronal cells. We investigated the effects of cilnidipine on N-type Ca2+ channels in IMR-32 human neuroblastoma cells using fura-2-based microfluorimetry. The ratio of the intensities of the emitted fluorescence at an excitation wavelength of 340 nm to that at 380 nm was calibrated to estimate the intracellular concentration of Ca2+. Stimulation of IMR-32 cells by 40 mmol/l KCl immediately increased the intensities ratio. In the presence of 10 micromol/l of nifedipine to block L-type Ca2+ channels, omega-conotoxin GVIA, a selective N-type Ca2+ channel blocker, in a concentration of 1 micromol/l suppressed the elevation of the intensities ratio induced by 40 mmol/l KCl. Similarly, cilnidipine in a concentration of 10 micromo/l suppressed the elevation of the ratio induced by 40 mmol/l KCl, and this suppression was effectively inhibited after the treatment with omega-conotoxin GVIA. These results suggest that cilnidipine potentially inhibits N-type Ca2+ channels in human neuronal cells and might be applied as a prospective therapeutic tool to provide neuronal protection as well as its antihypertensive effects and anti-sympathetic actions.
Takahara
Akira
A
Pharmaceutical Research Laboratories, Pharmaceuticals Company, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan. akira_takahara@ajp.co.jp
Fujita
Shin-ichi
S
Moki
Keiko
K
Ono
Yukitsugu
Y
Koganei
Hajime
H
Iwayama
Satoshi
S
Yamamoto
Hiroshi
H
D000959:Antihypertensive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D018929:Cell Culture Techniques; D004095:Dihydropyridines / Q000494:pharmacology*; D005434:Flow Cytometry; D016257:Fura-2; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; C065927:cilnidipine; D002118:Calcium; D016257:Fura-2