Age-related alterations in pre-synaptic and receptor-mediated cholinergic functions in rat brain.
Fractional [3H]acetylcholine (ACh) release and regulation of release process by muscarinic receptors were studied in corpus striatum of young and aged rat brains. [3H] Quinuclidinyl benzilate (QNB) binding and carbachol stimulated phosphoinositide turnover, on the other hand, were compared in striatal, hippocampal and cortical tissues. High potassium (10 mM)-induced fractional [3H]ACh release from striatal slices was reduced by aging. Although inhibition of acetylcholinesterase with eserine (20 microM) significantly decreased stimulation-induced fractional [3H]ACh release in two groups of rats, this inhibition slightly lessened with aging. Incubation of striatal slices with muscarinic antagonists reversed eserine-induced inhibition in fractional [3H]ACh release with a similar order of potency (atropine = 4-DAMP > AF-DX 116 > pirenzepine) in young and aged rat striatum, but age-induced difference in stimulated ACh release was not abolish by muscarinic antagonists. These results suggested that fractional [3H]ACh release from striatum of both age groups is modulated mainly by M3 muscarinic receptor subtype. Although both muscarinic receptor density and labeling of inositol lipids with [myo-3H]inositol decreased with aging, carbachol-stimulated [3H]myo inositol-1-fosfat (IP1) accumulation was found similar in striatal, cortical and hippocampal slices.
Büyükuysal
R L
RL
Uludag University, Medical Faculty, Department of Pharmacology Görükle Kampüsü, Bursa, Turkey.
Ulus
I H
IH
Kiran
B K
BK
D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009928:Organ Specificity; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010830:Physostigmine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D008563:Membrane Lipids; D018727:Muscarinic Antagonists; D010716:Phosphatidylinositols; D010743:Phospholipids; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D010830:Physostigmine; D000109:Acetylcholine