Decreased carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation in senescent rat cerebral cortical slices

Abstract

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)P 4]. Ins(1,34,5)P 4 appears to have second messenger functions. To investigate the effects of aging on agonist stimulated Ins(1,3,4,5)P 4 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]InsP 3) and [ 3h]Ins(1,3,4,5)P 4 formation in young and old rat cerebral cortical slices. Norepinephrine, 5-hydroxytryptamine, and vasopressin failed to stimulate [ 3H]Ins(1,3,4,5)P 4 or [ 3H]InsP 3 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)P 4 formation was reduced by 44%. Angiotensin II stimulated [ 3H]InsP 3 was increased (21%) 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.