TY - JOUR
T1 - Inositol trisphosphate receptor localization in brain
T2 - variable stoichiometry with protein kinase C
AU - Worley, Paul F.
AU - Baraban, Jay M.
AU - Colvin, Jennifer S.
AU - Snyder, Solomon H.
PY - 1987
Y1 - 1987
N2 - 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
AB - 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
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U2 - 10.1038/325159a0
DO - 10.1038/325159a0
M3 - Article
C2 - 3027583
AN - SCOPUS:0023140521
SN - 0028-0836
VL - 325
SP - 159
EP - 161
JO - Nature
JF - Nature
IS - 6100
ER -