AGE-RELATED ALTERATIONS IN PRESYNAPTIC AND RECEPTOR-MEDIATED CHOLINERGIC FUNCTIONS IN RAT-BRAIN

Fractional [H-3]acetylcholine (ACh) release and regulation of release process by muscarinic receptors were studied in corpus striatum of you ng and aged rat brains. [H-3] Quinuclidinyl benzilate (QNB) binding an d carbachol stimulated phosphoinositide turnover, on the other hand, w ere compared in striatal, hippocampal and cortical tissues. High potas sium (10 mM)-induced fractional [H-3]ACh release from striatal slices was reduced by aging. Although inhibition of acetylcholinesterase with eserine (20 mu M) significantly decreased stimulation-induced fractio nal [H-3]ACh release in two groups of rats, this inhibition slightly l essened with aging. Incubation of striatal slices with muscarinic anta gonists reversed eserine-induced inhibition in fractional [H-3]ACh rel ease with a similar order of potency (atropine = 4-DAMP > AF-DX 116 > pirenzepine) in young and aged rat striatum, but age-induced differenc e in stimulated ACh release was not abolish by muscarinic antagonists. These results suggested that fractional [H-3]ACh release from striatu m of both age groups is modulated mainly by M-3, muscarinic receptor s ubtype. Although both muscarinic receptor density and labeling of inos itol lipids with [myo-H-3]inositol decreased with aging, carbachol-sti mulated [H-3]myo inositol-1-fosfat (IF1) accumulation was found simila r in striatal, cortical and hippocampal slices.