METABOLIC KINETICS OF BRAIN MUSCARINIC CHOLINERGIC RECEPTORS IN NORMAL AND HYPOTHYROID MICE

METABOLIC KINETICS OF BRAIN MUSCARINIC CHOLINERGIC RECEPTORS IN NORMAL AND HYPOTHYROID MICE 1 first-author 1 1 1 Shanghai Second Medical University, Shanghai 200025, China Shanghai Second Medical University, Shanghai 200025, China A technique for studying in vivo the production rate and turnover rate constant of mouse brain M-receptors was established. A single injection of 25 mg / kg of Benzilylcholine Mustard to living mice resulted in 90 % irreversible block of brain M-receptors. The time course of the receptor density was then monitored by 3 H-QNB binding assay and the production rate and turnover rate constant were calculated from the time course curve with a computer program. It was found that in normal mice the turnover rate constant was about 0.035 h -1 (half-life was about 20 h) and the production rate was 30-42 fmol / (h · mg protein). Parallel experiments revealed a significant slow down of the turnover of brain M-receptors in hypothyroid mice (turnover rate constant was 0.0257±0.0012 h -1 in hypothyroid vs. 0.0356 ± 0.0021 h -1 in normal) while the production rate was not changed significantly. The results suggest that thyroid hormones have a regulatory action on the turnover of brain M-receptors and the elevation of brain M-receptor density together with slow down of the turnover of brain M-receptors is probably one of the important mechanisms relevant to the brain dysfunction in hypothyroidism. Hypothyroidism Muscarinic cholinergic receptor Benzilylcholine mustard (BCM) Metabolic kinetics of M-receptor Brain M-receptor REFERENCES DeGroot L J , Larsen P R , Refetoff S et al . The thyroid and its disease . 5th ed. New York : John Wiley and Sons , 1984 ; 574 The thyroid and its disease Megaugh J L . Ann Rev Neurosci , 1989 ; 12 : 255 Ann Rev Neurosci Pepeu G . Pharmacol Res Commun , 1988 ; 20 : 91 Pharmacol Res Commun Berger M , Fleckensten P , Riemann D et al . In: Bunney W E , Hippius H , Laakman G et al . eds. Neuropsycho-pharmacology . Berlin : Springer Verlag , 1990 ; 208 Neuropsycho-pharmacology Gharma V K , Banerjee S P . J Biochem , 1977 ; 252 : 7444 J Biochem Patel A J , Smith R M , Kingsburg A E et al . Brain Res . 1980 ; 198 : 389 Brain Res Kastrup J , Christensen N J . Scand J Clin Lab Invest , 1984 ; 44 : 33 Scand J Clin Lab Invest Gill E W , Rang H G . Mol Pharmacol , 1966 ; 2 : 284 Mol Pharmacol Yamamura H I , Snyder S H . Proc Natl Acad Sci USA , 1974 ; 71 : 1725 Proc Natl Acad Sci USA Schlief R F , Wensink P C . Practical methods in molecular biology . New York : Springer-Verlag , 1981 ; 75 Practical methods in molecular biology Hunter D D , Nathanson N M . J Neuroscience , 1986 ; 6 : 3739 J Neuroscience Xia Zongqin . Nucl Sci Techniq , 1990 ; 1 : 161 Nucl Sci Techniq Reed B C , Lane D M . Proc Natl Acad Sci , 1980 ; 77 : 285 Proc Natl Acad Sci Diem K , Lentner C eds. Scientific tables , 7th ed . Basel : Ciba-Geigy , 1971 ; 178 Scientific tables Mahan L C , Mckeman R M , Insel P A et al . Ann Rev Pharmacol Toxicol , 1987 ; 27 : 215 Ann Rev Pharmacol Toxicol Siegek H , Triggle D J . Life Sciences , 1982 ; 30 : 1645 Life Sciences Christophe J , Neef P D , Robberecht P R . Br J Pharmacol , 1986 ; 88 : 63 Br J Pharmacol Rang H P . Ann New York Acad Sci , 1967 ; 144 : 756 Ann New York Acad Sci Waisberg M , Shainberg A . Biochem Pharmacol , 1992 ; 41 : 2327 Biochem Pharmacol Muller W E . Acta Psychiatr Scand . 1991 ; Suppl. 366 : 5 Acta Psychiatr Scand Spiegel R . Acta Psychiatr Scand , 1991 ; Suppl. 366 : 66 Acta Psychiatr Scand 1993-11-01 2021-02-05 1993 Nuclear Science and Techniques 4 4