The present address of Dr. R. V. Bhat is Department of Neuroscience, Johns Hopkins University, School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, U.S.A.
Effects of Chronic Nicotine Infusion on Kinetics of High-Affinity Nicotine Binding
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 62, Issue 2, pages 574–581, February 1994
How to Cite
Bhat, R. V., Marks, M. J. and Collins, A. C. (1994), Effects of Chronic Nicotine Infusion on Kinetics of High-Affinity Nicotine Binding. Journal of Neurochemistry, 62: 574–581. doi: 10.1046/j.1471-4159.1994.62020574.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received March 31, 1993; revised manuscript received June 28, 1993; accepted June 29, 1993.
- Nicotinic receptors;
Abstract: It is well established that chronic nicotine treatment produces a dose-dependent increase in high-affinity l-[3H]nicotine binding. This increase may be due to chronic desensitization of the receptor. Sophisticated kinetic analyses of high-affinity nicotine binding to rat brain have demonstrated that the association rate is biphasic; the fast phase may represent binding to a high-affinity predesensitized state and the slow phase may represent binding to a lower affinity ground state that then isomerizes to form the high-affinity binding site. This isomerization presumably leads to receptor desensitization. The studies reported here assessed whether binding to mouse brain nicotinic receptors shows these same properties and whether chronic intravenous infusion of nicotine results in changes in these kinetic properties. The results obtained indicate that mouse brain nicotine binding also shows biphasic association kinetics and uniphasic dissociation kinetics, which supports the assertion that the receptor exists in two interconvertible states. However, unlike other results obtained with rat brain, the rate of the slow association process did not change with ligand concentration. Chronic infusion resulted in a dose-dependent increase in l-[3H]-nicotine binding, but the ratio of fast/slow phases of binding was not changed by these treatments. These results suggest that chronic infusion does not alter measurably the kinetics of nicotinic receptor binding when measured in vitro.