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1 Department of Pharmacology, Harvard Medical School, Boston, Massachvsetts
Evidence for the existence of muscarinic as well as nicotinic receptor sites was sought in experiments in open-chest spinal dogs. Acetylcholine was injected into the right subclavian artery to reach the sympathetic cardiac ganglia. Heart rate increase was used as indicator of ganglionic stimulation. Dose-response curves for i.a. acetyicholine vs heart rate were obtained. Hexamethonium (10-30 mg/kg) and other "nicotinic" antagonists (d-tubo curarine, mecamylamine and chlorisondamine) affected this curve very little and increased the maximally obtainable response. Atropine (0.01-3.0 mg/kg) and scopolamine caused a small shift to the right (dose ratio, about 3). Atropine, given in divided doses after a prior "loading" dose of hexamethonium or similar agent, caused dose-dependent shifts of the acetylcholine dose-response curves to the right (dose ratio with 0.1 mg/kg of atropine, about 20). Hexamethonium, after a prior loading dose of atropine, shifted the dose-response curve stepwise to the right (dose ratio with 10 mg/kg of hexamethonium, 5-10). This work confirms the presence of muscarinic receptors in cardiac sympathetic ganglia of the dog postulated previously on the basis of nerve stimulation experiments.
Submitted on January 24, 1969
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