title: Effect of aging on myo-inositol and phosphoinositide metabolism in the cochlear and vestibular sensory epithelia of the rat.
abstract: Neurotransmission and transmembrane signaling are among the cellular mechanisms affected in the aging nervous system. In the inner ear, the phosphoinositide second messenger cascade is of particular interest as a target of the aging process. In both the cochlear (CSE) and vestibular sensory epithelia (VSE), the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) to the second messenger inositol 1,4,5-trisphosphate (InsP3) is coupled to muscarinic cholinergic and P2y purinergic receptors and may be linked to calcium homeostasis. The present study compared the turnover of phosphoinositides (PtdInsPs), receptor-mediated release of inositol phosphates (InsPs), and concentrations of endogenous myo-inositol in the CSE and VSE of young (3 months) and aged (24 months) Fischer-344 rats. In the aged rat, there was a significant increase in [3H]inositol incorporation (per mass of protein) into PtdInsPs plus InsPs in both sensory epithelia while the protein content remained unchanged. In contrast, no age-dependent differences were found when pre-labeled [3H]PtdInsPs were 'chased' with non-radiolabeled myo-inositol indicating that the turnover of these lipids was unaffected. The cholinergic receptor agonist carbamylcholine and the P2 purinergic receptor agonist adenosine 5'-O-(3-thiotriphosphate) stimulated the release of [3H]InsPs two- to six-fold in both organs. This agonist-stimulated release of [3H]InsPs (per mass of protein) was significantly higher in aged animals. However, when the same stimulation was expressed as per cent of control values, there was no age-dependent difference.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506.
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: J
authors.initials: J
authors.lastname: McLaren
authors.forename: J
authors.initials: J
authors.lastname: Schacht
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002217:Carbachol / Q000494:pharmacology; D003051:Cochlea / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015290:Second Messenger Systems; D014722:Vestibule, Labyrinth / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D010716:Phosphatidylinositols; C022571:adenosine 5'-O-(3-thiotriphosphate); D007294:Inositol; D000255:Adenosine Triphosphate; D002217:Carbachol