IBMX induces calcium release from intracellular stores in rat sensory neurones.
The intracellular free calcium concentration ([Ca2+]i) was recorded from freshly isolated rat dorsal root ganglia (DRG) neurones by means of Fura-2 or Indo-1-based microfluorimetry. Extracellular application of IBMX at millimolar concentrations evoked transient elevations in [Ca2+]i. The amplitude and rate of rise of the [Ca2+]i transient increased with increasing IBMX concentration. The effects of IBMX on [Ca2+]i were not mimicked by direct manipulation of the intracellular level of cyclic nucleotides, nor incubation with dibutyryl-cAMP, cGMP or 8-bromo-cGMP; neither did treatment with forskolin induce similar [Ca2+]i transients. The IBMX-evoked [Ca2+]i elevation persisted in Ca(2+)-free extracellular solutions, suggesting its origination was from intracellular stores. Caffeine-induced depletion of internal Ca2+ pool prevented IBMX-evoked [Ca2+]i responses, and vice versa, IBMX treatment strongly reduced the amplitude of subsequent caffeine-induced [Ca2+]i elevation. Both ryanodine and procaine, agents known to interact with Ca(2+)-gated Ca2+ release channels of the intracellular endoplasmic reticulum calcium stores, effectively inhibited IBMX-induced [Ca2+]i transients. We suggest that, in addition to its known phosphodiesterase-inhibiting activity, IBMX is an effective liberator of Ca2+ from ryanodine/caffeine-sensitive internal calcium stores in neural cells.
Usachev
Y
Y
Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Verkhratsky
A
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D013806:Theophylline / Q000494:pharmacology
D005576:Colforsin; C016276:8-bromocyclic GMP; D003995:Dibutyryl Cyclic GMP; D002110:Caffeine; D003994:Bucladesine; D013806:Theophylline; D006152:Cyclic GMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine