Inositol trisphosphate receptor localization in brain: variable stoichiometry with protein kinase C

Research output: Contribution to journalArticle

Abstract

Many neurotransmitters, hormones and growth factors act at membrane receptors to stimulate the phosphodiesteratic hydrolysis of phosphatidyl- inositol 4,5-bisphosphate generating the co-messengers inositol 1,4,5-trisphosphate (Ins(l,4,5)P3) and diacylglycerol1,2. Diacylglycerol stimulates protein kinase C3 while Ins(l,4,5)P 3 is postulated to activate specific receptors leading to release of intracellular calcium4-9, probably from the endoplasmic reticulum10. In recent preliminary reports, Rubin and associates11-13 detected 32P-Ins(l,4,5)P3 binding to liver and adrenal microsomes and to permeabilized neutrophils and liver cells. We now report the biochemical and autoradiographic demonstration in brain of high affinity, selective binding sites for 3H- and 32P-labelled Ins(l,4,5)P3 at levels 100-300 times higher than those observed in peripheral tissues. The potencies of various myo-inositol analogues at the Ins(l,4,5)P3 binding site correspond to their potencies in releasing calcium from microsomes1, supporting the physiological relevance of this receptor. Brain autoradiograms demonstrate discrete, heterogeneous localizations of Ins(l,4,5)P3 receptors. In some regions localizations of Ins(l,4,5)P3 receptors resemble those of protein kinase C 14, while in others they differ markedly, suggesting a novel mechanism whereby the relative activity of the two limbs of the PI cycle can be differently regulated

Original languageEnglish (US)
Pages (from-to)159-161
Number of pages3
JournalNature
Volume325
Issue number6100
DOIs
StatePublished - Dec 1 1987

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