NTP, the photoproduct of nifedipine, activates caffeine-sensitive ion channels in leech neurons.
Leech P neurons possess caffeine-sensitive ion channels in intracellular Ca(2+) stores and in the plasma membrane. The following results indicate that these channels are also activated by 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester (NTP), the photoproduct of the L-type Ca(2+) channel-blocker nifedipine: (1) Just like caffeine, NTP evoked Ca(2+) influx and intracellular Ca(2+) release, as well as the influx of various other divalent cations and that of Na(+). (2) In the presence of high NTP or caffeine concentrations the plasma membrane channels close, suggesting desensitization of the channel-activating mechanism. (3) Depending on the concentration, NTP and caffeine induce cross-desensitization or act additively. (4) NTP was effective in the same neurons as caffeine (P, N, Leydig, 101), and it was ineffective in neurons in which caffeine was also ineffective (AP, T, L, 8, AE). (5) In Retzius neurons, NTP and caffeine evoked intracellular Ca(2+) release but no Ca(2+) influx. Despite these parallels, the effects of NTP and caffeine were not identical, which may be due to differences in the mechanisms of channel activation or desensitization and/or to substance-specific side effects. The caffeine-sensitive ion channels were activated by NTP concentrations > or =10 microM, which is almost three orders of magnitude smaller than the threshold concentration of caffeine.
Schoppe
Jürgen
J
Institut für Neurobiologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, Geb. 26.02, D-40255, Düsseldorf, Germany.
Dierkes
Paul W
PW
Hochstrate
Peter
P
Schlue
Wolf R
WR
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000378:metabolism*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007865:Leeches / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007473:Ion Channels; D002110:Caffeine; C065818:2,6-dimethyl-4-(2'-nitrosophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; D009543:Nifedipine; D002118:Calcium