Effects of Anticholinesterase Exposure on Transport and Distribution of High vs. Low Affinity Muscarinic Cholinergic Receptors

摘要

Axonal transport of muscarinic cholinergic receptors has been demonstrated in the brain. The receptors in reference emanate from the septum and are transported through the fimbria to the hippocampal formation. These muscarinic receptors represent presynaptic autoreceptors in the cholingeric projection from the medial septum to the hippocampus. The overall density of muscarinic receptors in the hippocampus is only slightly increased after a septal lesion, but this small increase represents a loss of high affinity agonist binding sites which is overshadowed by a dramatic increase in the low affinity agonist state of the receptor found in several hippocampal regions. This same shift in muscarinic receptor agonist affinity states is seen in lumbar levels of the cat spinal cord following transection of the cord at cervical levels. Chronically thiamine deficient laboratory rats also exhibit a shift in the agonist state of the muscarinic receptor to that of a lower affinity except in the ventromedial hypothalamus where an overall decrease in density is manifest. Methodology for direct labeling of high affinity muscarinic agonist receptors has been perfected using the agonist cis methyldioxolane. These sites have been localized autoradiographically. Subtypes of muscarinic antagonist sites have also been localized using a tritiated form of the atypical antagonist pirenzepine. Thus, it will be possible to localize several different muscarinic cholinergic receptor subtypes in animals chronically exposed to anticholinergics or anticholinesterases. It will also be possible to study the effects of this exposure on axonal transport of muscarinic receptors in the brain.