Chronic nicotine treatment upregulates muscarinic M(1)-receptors in the rat stomach

This study examines the hypothesis that gastric muscarinic receptor supersensitivity which follows partial vagal ganglion block by chronic nicotine administration, and which accounts for the observed time- and dose-dependent worsening effect of the alkaloid on cold-restraint stress-induced gastric ulcers in rats, could be due to muscarinic receptor upregulation. Samples of homogenised gastric glandular mucosae of rats given 0, 5 or 50 mu g nicotine mL(-1) drinking water for 10 days were tested for muscarinic receptor activity using [H-3] pirenzepine radioligand binding. Radioactivity in the filtered fraction was measured, and specific binding was calculated from the difference between total binding and binding in the presence of atropine. Binding capacity (B-max) was dose-dependently increased in the two nicotine-treated groups, but receptor affinity (K-D) was unchanged. These novel findings indicate that gastric muscarinic receptor supersensitivity consequent to chronic nicotine treatment is largely due to gastric M(1)-receptor upregulation.