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

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 μ M ) on nicotine‐induced relaxations of longitudinal muscle strips of rat gastric fundus. In the presence of 1 μ M atropine and 3 μ M guanethidine, nicotine (30 μ M ) 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 μ M ). One μ M tetrodotoxin (TTX) completely blocks this nicotine‐induced relaxation. High concentrations of guanethidine (10 μ M ), but not adrenoceptor blockade by the α‐adrenoceptor antagonist phentolamine in combination with the β‐adrenoceptor antagonist nadolol (both 3 μ M ), inhibit the nicotine‐induced relaxation. Guanethidine (0.1–100 μ M ) has no effect on relaxations induced by electrical field stimulation (EFS; 1–8 Hz), nitric oxide (NO; 0.01–1 μ M ), vasoactive intestinal polypeptide (VIP; 0.1–10 n M ) or isoprenaline (1–10 n M ). We conclude that high concentrations of guanethidine (10 μ M ) 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