Nicotinic acetylcholine receptor blocking effect of guanethidine in the rat gastric fundus

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Abstract
Guanethidine is commonly used as a drug to investigate adrenergic neurotransmission and, in combination with atropine, to realize non‐adrenergic non‐cholinergic (NANC) conditions. Previous studies suggested a nicotinic acetylcholine receptor blocking effect of guanethidine. Therefore, we investigated the effect of increasing concentrations of guanethidine (0.1–100 μM) on nicotine‐induced relaxations of longitudinal muscle strips of rat gastric fundus. In the presence of 1 μM atropine and 3 μM guanethidine, nicotine (30 μM) induces a fast and sustained relaxation which is partly inhibited by the nitric oxide synthase inhibitors Nω‐nitro‐L‐arginine (L‐NOARG) and Nω‐nitro‐L‐arginine methyl ester (L‐NAME) (both 30 and 100 μM). One μM tetrodotoxin (TTX) completely blocks this nicotine‐induced relaxation. High concentrations of guanethidine (10 μM), but not adrenoceptor blockade by the α‐adrenoceptor antagonist phentolamine in combination with the β‐adrenoceptor antagonist nadolol (both 3 μM), inhibit the nicotine‐induced relaxation. Guanethidine (0.1–100 μM) has no effect on relaxations induced by electrical field stimulation (EFS; 1–8 Hz), nitric oxide (NO; 0.01–1 μM), vasoactive intestinal polypeptide (VIP; 0.1–10 nM) or isoprenaline (1–10 nM). We conclude that high concentrations of guanethidine (10 μM) block nicotine‐induced NANC relaxations of longitudinal muscle strips of the rat gastric fundus most likely at the level of the nicotinic acetylcholine receptor. British Journal of Pharmacology (1999) 128, 903–908; doi:10.1038/sj.bjp.0702865