Non-adrenergic non-cholinergic (NANC) inhibitory nerves have been described in all regions of the gastrointestinal tract, but have not been shown previously in the human gall bladder. Electrical field stimulation was used in the presence of various agonists and antagonists to show NANC inhibitory innervation in strips of human gall bladder muscle. Gall bladder strips were set up isometrically in an organ bath containing oxygenated Krebs's solution. Electrical field stimulation was applied at 10 Hz, pulse width 0.3 ms and supramaximal voltage at intervals of 3 to 5 minutes. Of 60 strips that contracted in response to electrical field stimulation, 30 showed relaxation on electrical field stimulation in the presence of either carbachol (5-10 microM) or else atropine (0.5-2 microM) plus cholecystokinin octapeptide (0.01-0.1 microM) or caerulein (0.1 nM) or histamine (5-10 microM). In 22 strips this relaxation was not abolished by guanethidine (2-5 microM) showing the NANC nature of this response. The NANC relaxation was abolished by L-nitroarginine (100 microM) and this effect was partly reversible by L arginine (200 microM). All responses to electrical field stimulation were abolished by tetrodotoxin (0.2-2 microM). These results show for the first time a NANC inhibitory innervation in human gall bladder muscle. The probable neurotransmitter is nitric oxide.
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