Formation and actions of calcium-mobilizing messenger, inositol 1,4,5-trisphosphate.
A variety of surface membrane receptors can activate a phospholipase C, which degrades phosphatidylinositol 4,5-bisphosphate liberating a calcium mobilizing second messenger, inositol 1,4,5-trisphosphate [(1,4,5)IP3]. The coupling of surface receptors to the phospholipase C involves one or more guanine nucleotide-dependent regulatory proteins that are similar but not identical to those that regulate adenylate cyclase. (1,4,5)IP3 has been shown to release Ca2+ from a portion of the endoplasmic reticulum and is believed responsible for the initial phase of Ca2+ mobilization ascribed to internal Ca2+ release. (1,4,5)IP3 acts by binding to a specific receptor that either is a component of, or regulates, a Ca2+ ion channel. The release of Ca2+ from the (1,4,5)IP3-sensitive component of the endoplasmic reticulum may secondarily activate the second phase of Ca2+ mobilization, which involves Ca2+ entry. (1,4,5)IP3 is metabolized by two pathways. One involves the action of a 5-phosphatase that degrades (1,4,5)IP3 to inositol 1,4-bisphosphate, whereas the other involves a 3-kinase that phosphorylates (1,4,5)IP3 to produce inositol 1,3,4,5-tetrakisphosphate. The significance of this dual metabolism is not known, but it may be important in rapidly extinguishing the Ca2+-releasing activity (1,4,5)IP3.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D004721:Endoplasmic Reticulum / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium