Nicotinic acetylcholine receptor blocking effect of guanethidine in the rat gastric fundus.
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.
Blommaart
P J
PJ
Division of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Ferwerda
G
G
Kodde
A
A
Tytgat
G N
GN
Boeckxstaens
G E
GE
D000818:Animals; D004558:Electric Stimulation; D005748:Gastric Fundus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006145:Guanethidine / Q000494:pharmacology*; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D006145:Guanethidine