In vitro and in vivo modulation of cholinergic muscarinic receptors in rat lymphocytes and brain by cholinergic agents.
Costa-LG; Kaylor-G; Murphy-SD
Int J Immunopharmacol 1990 Jan; 12(1):67-75
The in-vitro and in-vivo modulation of muscarinic receptors by cholinergic drugs was investigated in Sprague-Dawley-rat lymphocytes and brain. Splenic lymphocytes were incubated with oxotremorine or other cholinergic agents at 4 or 37 degrees-C, and then binding of tritiated quinuclidinyl-benzilate (QNB) was determined. For in-vivo studies, oxotremorine and atropine-sulfate were administered to rats at 20mg/kg for 14 days using an implanted minipump; disulfoton was administered intraperitoneally at 2mg/kg per day for 14 days. Lymphocytes were isolated from the spleen and the blood, and QNB binding was assayed. QNB binding was also assayed in brain membranes. The major finding was that muscarinic receptors present on lymphocytes can be modulated in-vitro and in-vivo by cholinergic compounds. In-vitro incubation of lymphocytes caused a time and concentration dependent decrease in the density of muscarinic receptors, which was antagonized by coincubation with atropine. A maximal decrease of 60 to 70% was noted 2 to 3 hours after incubation at 37 degrees. No alterations were noted in tritium labeled QNB binding, suggesting that the observed decrease was not an artifact due to residual, unwashed oxotremorine, but was due rather to a possible desensitization or down regulation of muscarinic receptors. In-vivo treatment caused a decrease of QNB binding in the brain. Repeated exposure to the disulfoton caused significant inhibition of cholinesterase activity in cerebral cortex and hippocampus (86 to 88%), lymphocytes (59%), plasma (68%), and erythrocytes (70%). The authors suggest that lymphocytes may be useful as markers for cholinergic muscarinic receptors in nerve tissue.
NIOSH-Publication; NIOSH-Grant; Grants-other; Central-nervous-system; Biological-monitoring; Organo-phosphorus-compounds; Enzyme-activity; In-vivo-studies; In-vitro-studies
Environmental Health University of Washington Dept of Environ Hlth, SC-34 Seattle, WA 98195
International Journal of Immunopharmacology
University of Washington, Seattle, Washington