Effects of nBM lesions on muscarinic-stimulation of phosphoinositide hydrolysis.
The nucleus basalis magnocellularis (nBM) is believed to be the major path of cholinergic innervation to the frontal cortex. The cerebral cortex is known to contain muscarinic receptors that are coupled to the hydrolysis of phosphoinositides (PI) (9,14). Adult male Sprague-Dawley rats were unilaterally and bilaterally lesioned at the nBM with the excitotoxin ibotenic acid and killed at 7 or 21 to 23 days postsurgery. In rats unilaterally lesioned 7 days previously, the carbachol dose-response curves in lesioned fronto-parietal cortex were identical to control fronto-parietal cortices. In rats studied 21 to 23 days postsurgery, carbachol dose-response curves were again identical in control vs. lesioned fronto-parietal cortices. Similar results are obtained when bilaterally lesioned rats are compared to sham-operated controls. For each group, the hydrolysis is linear with respect to time until 15 minutes with a maximum reached at approximately 40 minutes. Receptor density, as measured by [3H]-QNB binding or agonist competition for [3H]-QNB binding, was not changed by any of the lesions studied. These results suggest that the loss of cholinergic innervation from the nBM does not result in compensatory denervation supersensitivity in cerebral fronto-parietal cortical muscarinic receptors.
Raulli
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Department of Pharmacology, University of Florida College of Medicine, Gainesville 32610.
Arendash
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Crews
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D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D003714:Denervation; D006868:Hydrolysis; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013377:Substantia Innominata / Q000502:physiology*
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol