Distribution of Neurotoxic Esterase in Rat and Hen Brain: Relation to Alpha(2) Adrenoreceptors in Rat Brain.

Neurotoxic esterase (NTE) is an enzyme which is present in nervous and other tissues. Certain organophosphorus inhibitors of this enzyme produce a delayed neuropathy when administered to sensitive species. The normal function and the natural substrates for this enzyme are unknown. Furthermore, little is known about the distribution of this enzyme within the nervous system of the hen, a sensitive species which has been studied extensively, or the rat, a species relatively insensitive to the delayed neuropathic effects of organophosphorus inhibition. The objectives of this dissertation were: (a) to determine the distribution of neurotoxic esterase in the rat nervous system; (b) to compare the distribution of this enzyme in the rat with that in the hen; (c) to ascertain the relationship of neurotoxic esterase to the alpha(,2) adrenoreceptor, an autoreceptor located upon nerve terminals which regulates the release of neurotransmitter substances; and (d) to measure the effects upon alpha(,2) adrenoreceptors of triorthocresyl phosphate, a neurotoxic esterase inhibitor, paraoxon, a non-neurotoxic cholinesterase inhibitor and oxotremorine, a centrally active muscarinic agonist. The present studies show that: (a) neurotoxic esterase is distributed unevenly in both the rat and hen brain; (b) inhibitor-resistant esterase is distributed evenly throughout most areas of the brains of the two species; (c) no correlation exists between the distribution of neurotoxic esterase and acetylcholinesterase in the brains of either species; and (d) triorthocresyl phosphate treatment increases the number of alpha(,2) adrenoreceptors in the rat amygdala, hippocampus and brainstem. Oxotremorine and paraoxon also increase the number of these receptors in the brainstem. In contrast, oxotremorine decreased the number of alpha(,2) adrenoreceptors in other areas of the rat brain. These observations are consistent with the hypothesis that neurotoxic esterase is an enzyme involved in the regulation of adrenorecptor function.PhDPublic healthUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/159391/1/8314291.pd