Interactions of the ulcerogen cysteamine with enteric inhibitory nerves and putative transmitters in the rat small intestine.

1. The effects of the ulcerogen cysteamine (2-aminoethanethiol HCL) on spontaneous activity and evoked responses of rat isolated small intestine preparations were investigated in vitro. 2. Cysteamine induced concentration-dependent relaxations of isolated segments of the rat duodenum, jejunum and ileum. These actions were manifest simultaneously in both the circular and longitudinal muscle layers, where the responses displayed a similar profile. 3. Treatment with tetrodotoxin (0.1 microM) or cold storage of individual preparations to prevent nerve-mediated responses abolished the effects of cysteamine. The presence of atropine (0.1 microM), propranolol (3.0 microM) and phentolamine (3.0 microM) in the bathing solution did not affect the cysteamine-evoked relaxations, suggesting cysteamine was stimulating non-adrenergic, non-cholinergic (NANC) intrinsic inhibitory nerves. 4. Applied cysteamine reversibly reduced GABA- and DMPP-evoked NANC nerve-mediated relaxations via actions unrelated to the receptors for these agents. 5. Methysergide-sensitive (direct) actions of 5-HT on the muscularis but not 5-HT neurally evoked responses were blocked by cysteamine. 6. It would appear that cysteamine has excitatory and inhibitory actions on enteric inhibitory nerves as well as specifically interfering with myogenic but not neural actions of 5-HT.