The pharmacology of intracellular Ca(2+)-release channels

Trends Pharmacol Sci. 1994 May;15(5):145-9. doi: 10.1016/0165-6147(94)90074-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Caffeine / metabolism
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / chemistry*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Calmodulin-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Heparin / metabolism
  • Heparin / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors
  • Muscle Proteins / drug effects
  • Muscle Proteins / metabolism*
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Ryanodine Receptor Calcium Release Channel


  • Calcium Channels
  • Calmodulin-Binding Proteins
  • Inositol 1,4,5-Trisphosphate Receptors
  • Muscle Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Ryanodine Receptor Calcium Release Channel
  • Caffeine
  • Inositol 1,4,5-Trisphosphate
  • Heparin
  • Calcium