Modulation by nicotine on binding of cerebral muscarinic receptors with muscarinic agonist and antagonist.

AIM

To study the modulatory effects of nicotine on the binding of brain muscarinic receptors.

METHODS

The binding of brain muscarinic receptors with the agonist [3H] oxotremorine-M or the antagonist l-[3H]QNB was determined in the presence/absence of nicotine.

RESULTS

Pre-incubation of the membrane fraction derived from rat cerebral cortex with nicotine 1.0 mumol.L-1 led to a decrease in the dissociation constant (Kd) for [3H] oxotremorine-M binding to muscarinic receptors, while the maximal binding value (Bmax) was unchanged. The Kd value for binding of the muscarinic antagonist l-[3H]QNB was concentration-dependently increased by preincubation with nicotine 0.1 nmol.L-1-10.0 mumol.L-1, with Bmax unchanged. The effect of nicotine on the Kd for l-[3H]QNB binding was prevented by mecamylamine 10 nmol.L-1, but was enhanced by dithiothreitol 10 mumol.L-1, which by itself was also capable of increasing the Kd value.

CONCLUSION

Nicotine increases the affinity of brain muscarinic receptors for muscarinic agonist, but decreases the affinity of brain muscarinic receptors for muscarinic antagonist.