Decreased carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation in senescent rat cerebral cortical slices.
It is well established that muscarinic cholinergic receptors are linked to phosphoinositide hydrolysis in brain. Previous studies of muscarinic responses used Li+ to increase inositol phosphate accumulation and suggested little or no change during aging. Li+ disrupts certain aspects of the inositol phosphate metabolism and inhibits the formation of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. Ins(1,3,4,5)P4 appears to have second messenger functions. To investigate the effects of aging on agonist stimulated Ins(1,3,4,5)P4 formation, young (6-8 months) and old (28-30 months) Fischer 344 rat cerebral cortical or hippocampal slices were challenged with various agonists known to stimulate phosphoinositide hydrolysis in brain using a recently developed assay that does not use Li+. Carbachol and quisqualate stimulated [3H]inositol trisphosphate ([3H]InsP3) and [3H]Ins(1,3,4,5)P4 formation in young and old rat cerebral cortical slices. Norepinephrine, 5-hydroxytryptamine, and vasopressin failed to stimulate [3H]Ins(1,3,4,5)P4 or [3H]InsP3 formation in either young or old rat cerebral cortical slices. In old rat cerebral cortical slices, the carbachol-stimulated [3H]Ins(1,3,4,5)P4 formation was reduced by 44%. Angiotensin II stimulated [3H]InsP3 was increased (219%) in old rats. There was no influence of aging either on the basal level or on the maximal response to carbachol or quisqualate in hippocampal slices. These studies suggest region-specific changes in phosphoinositide hydrolysis during aging.
Kurian
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Department of Pharmacology, University of Florida College of Medicine, Gainesville 32610-0267.
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D000375:Aging / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008094:Lithium / Q000494:pharmacology; D008297:Male; D016318:Quisqualic Acid / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D000804:Angiotensin II; D016318:Quisqualic Acid; D002217:Carbachol; D008094:Lithium