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Tetrahydroaminoacridine is neurotrophic and promotes the expression of muscarinic receptor-coupled phosphoinositide turnover in differentiating cerebellar granule cells. 1993

K Sunaga, and D M Chuang, and R Ishitani
Group on Neuropharmacology, Josai University, Saitama, Japan.

We have investigated whether 9-amino-1,2,3,4-tetrahydroacridine (THA), a drug with potential antidementia activity, has a trophic action on differentiating cerebellar granule cells by using the method of [3H]inositol incorporation into inositol-containing phospholipid. Addition of THA (30-50 microM) prevented the extensive neuronal degeneration which occurred in the growth medium containing "low" K+ (15 mM). These effects were similar to the neuroprotective action caused by the presence of 100 microM N-methyl-D-aspartate (NMDA). Neurotrophic effects of THA and NMDA on cells grown in low K+ were also demonstrated by direct microscopic examination of cellular morphology. Measurement of phosphoinositide (PI) response in the rescued cells indicated that NMDA modestly promoted the PI response to carbachol and norepinephrine but markedly stimulated the activity induced by glutamate. In contrast, although THA had little or no influence on the maturation of the norepinephrine- and glutamate-induced PI response, it selectively enhanced the activity stimulated by carbachol. Furthermore, the THA treatment drastically increased the Vmax value of carbachol-induced PI turnover with no significant alteration in the EC50 value. Scatchard analysis of the binding of N-[3H]methylscopolamine to intact granule cells indicated a selective increase in the maximum binding value in cells grown in THA-supplementing medium. These observations suggest that THA seems to selectively up-regulate muscarinic cholinergic receptors.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010716 Phosphatidylinositols Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids. Inositide Phospholipid,Inositol Phosphoglyceride,Inositol Phosphoglycerides,Inositol Phospholipid,Phosphoinositide,Phosphoinositides,PtdIns,Inositide Phospholipids,Inositol Phospholipids,Phosphatidyl Inositol,Phosphatidylinositol,Inositol, Phosphatidyl,Phosphoglyceride, Inositol,Phosphoglycerides, Inositol,Phospholipid, Inositide,Phospholipid, Inositol,Phospholipids, Inositide,Phospholipids, Inositol
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
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
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D003594 Cytoplasmic Granules Condensed areas of cellular material that may be bounded by a membrane. Cytoplasmic Granule,Granule, Cytoplasmic,Granules, Cytoplasmic
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

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