The pharmacology of intracellular Ca(2+)-release channels.
Two classes of intracellular Ca(2+)-release channels, the ryanodine receptor and the inositol (1,4,5)-trisphosphate (IP3) receptor, are essential for spatio-temporal Ca2+ signalling in cells. Heparin and caffeine have been widely used to study these channels. It was originally thought that caffeine acts solely as an agonist for the ryanodine receptor and heparin acts solely as an inhibitor for the IP3 receptor. However, recent experiments indicate that these compounds have multiple effects, and are discussed in this review by Barbara Ehrlich and colleagues. In the same concentration range, caffeine activates the ryanodine receptor and inhibits the IP3 receptor, and heparin inhibits the IP3 receptor and activates the ryanodine receptor. More specific pharmacological tools that are suitable for studies of ryanodine and IP3 receptors are now beginning to emerge.
Ehrlich
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BE
Department of Medicine, University of Connecticut, Farmington 06032, USA.
Kaftan
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Bezprozvannaya
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Bezprozvanny
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D000818:Animals; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000187:drug effects; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009124:Muscle Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D002118:Calcium