Biomaterial Database

3-position modification of myo-inositol 1,4,5-trisphosphate: consequences for intracellular Ca2+ mobilisation and enzyme recognition. 1992

S T Safrany, and R A Wilcox, and C Liu, and B V Potter, and S R Nahorski

Department of Pharmacology and Therapeutics, University of Leicester, UK.

The ability of the novel D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) analogues, L-chiro-inositol 2,3,5-trisphosphate (L-ch-Ins(2,3,5)P3) and D-3-deoxy-3-fluoro-myo-inositol 1,4,5-trisphosphate (3F-Ins(1,4,5)P3), to bind to the Ins(1,4,5)P3 receptor, mobilise intracellular Ca2+ stores and interact with metabolic enzymes has been investigated. L-ch-Ins(2,3,5)P3 and 3F-Ins(1,4,5)P3 were bound by the Ins(1,4,5)P3 receptor from bovine adrenal cortex with relatively high affinity (Ki values 60.4 and 8.0 nM respectively) but with lower affinity than Ins(1,4,5)P3 (KD = 5.9 nM). Both analogues were apparent full agonists at the Ca2+ mobilising receptor in SH-SY5Y cells, but were less potent than Ins(1,4,5)P3 (EC50 L-ch-Ins(2,3,5)P3 = 1.4 microM, 3F-Ins(1,4,5)P3 = 0.37 microM and Ins(1,4,5)P3 = 0.12 microM). L-ch-Ins(2,3,5)P3 and 3F-Ins(1,4,5)P3 were resistant to Ins(1,4,5)P3 3-kinase, and were potent inhibitors of the enzyme (Ki values 7.1 and 8.6 microM respectively). 3F-Ins(1,4,5)P3 was hydrolysed by Ins(1,4,5)P3 5-phosphatase at a similar rate to Ins(1,4,5)P3, but inhibited dephosphorylation of [3H]Ins(1,4,5)P3 with high potency (apparent Ki = 3.9 microM) L-ch-Ins(2,3,5)P3 was also recognised by the enzyme with high affinity (Ki = 7.7 microM) but was resistant to hydrolysis. These results suggest that the environment around C-3 is of major importance for recognition not only by Ins(1,4,5)P3 3-kinase but also by Ins(1,4,5)P3 5-phosphatase.

UI	MeSH Term	Description	Entries
D009447	Neuroblastoma	A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)	Neuroblastomas
D010744	Phosphoric Monoester Hydrolases	A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate.	Phosphatase,Phosphatases,Phosphohydrolase,Phosphohydrolases,Phosphomonoesterase,Phosphomonoesterases,Phosphoric Monoester Hydrolase,Hydrolase, Phosphoric Monoester,Hydrolases, Phosphoric Monoester,Monoester Hydrolase, Phosphoric
D010770	Phosphotransferases	A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.	Kinases,Phosphotransferase,Phosphotransferases, ATP,Transphosphorylase,Transphosphorylases,Kinase,ATP Phosphotransferases
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004910	Erythrocyte Membrane	The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.	Erythrocyte Ghost,Red Cell Cytoskeleton,Red Cell Ghost,Erythrocyte Cytoskeleton,Cytoskeleton, Erythrocyte,Cytoskeleton, Red Cell,Erythrocyte Cytoskeletons,Erythrocyte Ghosts,Erythrocyte Membranes,Ghost, Erythrocyte,Ghost, Red Cell,Membrane, Erythrocyte,Red Cell Cytoskeletons,Red Cell Ghosts
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000311	Adrenal Glands	A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.	Adrenal Gland,Gland, Adrenal,Glands, Adrenal
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia