Increases in muscarinic stimulated hydrolysis of inositol phospholipids in rat hippocampus following cholinergic deafferentation are not parallelled by alterations in cholinergic receptor density.
The effect of electrolytic fimbria/fornix lesions on muscarinic receptor subtypes and putative nicotinic binding sites in the hippocampus has been studied using [3H]N-methylscopolamine, [3H]pirenzepine and [3H]L-nicotine, respectively. In parallel experiments the carbachol-stimulated hydrolysis of inositol phospholipids was measured after incorporation of [3H]inositol into hippocampal slice preparations. Ten days after lesioning there were no apparent changes in either receptor density or affinities despite extensive reductions in choline acetyltransferase. In contrast a significant increase in carbachol stimulated turnover of inositol phospholipids was measured. These observations suggest that whilst loss of cholinergic afferents may not affect receptor density per se, the efficacy of the post synaptic muscarinic receptors can be up-regulated at least in the short term.
Smith
C J
CJ
Department of Neuropathology, Newcastle General Hospital, U.K.
Court
J A
JA
Keith
A B
AB
Perry
E K
EK
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010890:Pirenzepine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012601:Scopolamine / Q000378:metabolism*
D010743:Phospholipids; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D007294:Inositol; D009538:Nicotine; D002217:Carbachol; D012601:Scopolamine