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  • Title: Nicotinic acetylcholine receptor blocking effect of guanethidine in the rat gastric fundus.
    Author: Blommaart PJ, Ferwerda G, Kodde A, Tytgat GN, Boeckxstaens GE.
    Journal: Br J Pharmacol; 1999 Oct; 128(4):903-8. PubMed ID: 10556924.
    Abstract:
    1 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 microM) on nicotine-induced relaxations of longitudinal muscle strips of rat gastric fundus. 2 In the presence of 1 microM atropine and 3 microM guanethidine, nicotine (30 microM) induces a fast and sustained relaxation which is partly inhibited by the nitric oxide synthase inhibitors Nomega-nitro-L-arginine (L-NOARG) and Nomega-nitro-L-arginine methyl ester (L-NAME) (both 30 and 100 microM). One microM tetrodotoxin (TTX) completely blocks this nicotine-induced relaxation. 3 High concentrations of guanethidine (> or =10 microM), but not adrenoceptor blockade by the alpha-adrenoceptor antagonist phentolamine in combination with the beta-adrenoceptor antagonist nadolol (both 3 microM), inhibit the nicotine-induced relaxation. 4 Guanethidine (0.1-100 microM) has no effect on relaxations induced by electrical field stimulation (EFS; 1-8 Hz), nitric oxide (NO; 0.01-1 microM), vasoactive intestinal polypeptide (VIP; 0.1-10 nM) or isoprenaline (1-10 nM). 5 We conclude that high concentrations of guanethidine (> or =10 microM) block nicotine-induced NANC relaxations of longitudinal muscle strips of the rat gastric fundus most likely at the level of the nicotinic acetylcholine receptor.
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