Bakich V, Brown J, Kwok Y N, McIntosh C, Nishimura E
Br J Pharmacol. 1984 Aug;82(4):791-800. doi: 10.1111/j.1476-5381.1984.tb16475.x.
Cysteamine (beta-mercaptoethylamine HCl) (1.0-40.0 mM) induced a concentration-dependent increase in tonic and phasic contractions of segments of guinea-pig ileum in vitro. Myenteric plexus-longitudinal muscle (MPLM) preparations also responded with an increase in tonic contractions but phasic contractions were either greatly reduced or absent, indicating that these were a response of the circular muscle. Atropine (5 microM) inhibited the cysteamine-induced contractions, whereas hexamethonium and guanethidine had no effect, suggesting that cysteamine was acting at least partly via a cholinergic mechanism involving muscarinic receptors. Tetrodotoxin increased the phasic contractions of ileal segments, but had no effect on the tonic component. Treatment of MPLM preparations with morphine (1 microM) resulted in a small reduction in responsiveness to cysteamine, and blocked electrically-induced contractions by at least 90%. Since morphine acts by inhibiting acetylcholine release via hyperpolarization of intrinsic neurones, a small but significant part of the cysteamine-induced contractions probably resulted from stimulation of acetylcholine release from intrinsic neurones. Following a response to high cysteamine concentrations (greater than 15 mM) tissues were refractory to subsequent cysteamine administration. Cross-desensitization between cysteamine and acetylcholine also occurred, as short-term (1-3 min) incubation of MPLM preparations with high concentrations of either compound (1-10 microM acetylcholine or 20 mM cysteamine) resulted in a reduced responsiveness to both. A reduced sensitivity to acetylcholine or cysteamine was obtained following long-term (45 min) incubation with acetylcholine (1 microM). Removal of Na+ from the incubation medium negated this effect. In contrast, the refractoriness to acetylcholine or cysteamine following long-term (45 min) incubation with cysteamine (20 mM) was accentuated in low Na+ medium. It is suggested that cysteamine induces a contraction of both the circular and longitudinal muscle of the guinea-pig ileum by stimulating the release of acetylcholine from intrinsic neurones, by an action at the level of the smooth muscle muscarinic receptor, and possibly by a non-cholinergic mechanism. However, the mechanisms by which acetylcholine and cysteamine induce tissue refractoriness probably differ.
半胱胺（β-巯基乙胺盐酸盐）（1.0 - 40.0 mM）可引起豚鼠离体回肠段张力性和相性收缩呈浓度依赖性增加。肠肌丛-纵行肌（MPLM）标本也出现张力性收缩增加，但相性收缩要么大幅减少要么消失，这表明这些是环行肌的反应。阿托品（5 microM）可抑制半胱胺诱导的收缩，而六甲铵和胍乙啶则无作用，提示半胱胺至少部分通过涉及毒蕈碱受体的胆碱能机制起作用。河豚毒素增加了回肠段的相性收缩，但对张力成分无影响。用吗啡（1 microM）处理MPLM标本导致对半胱胺的反应性略有降低，并使电诱导的收缩至少阻断90%。由于吗啡通过使内在神经元超极化来抑制乙酰胆碱释放起作用，半胱胺诱导的收缩中一小部分但显著部分可能是由于刺激了内在神经元释放乙酰胆碱。在对高浓度半胱胺（大于15 mM）产生反应后，组织对随后给予的半胱胺不再敏感。半胱胺和乙酰胆碱之间也发生交叉脱敏，因为将MPLM标本与高浓度的任何一种化合物（1 - 10 microM乙酰胆碱或20 mM半胱胺）短期（1 - 3分钟）孵育会导致对两者的反应性降低。与乙酰胆碱（1 microM）长期（45分钟）孵育后，对乙酰胆碱或半胱胺的敏感性降低。从孵育培养基中去除Na +可消除这种作用。相反，在低Na +培养基中，与半胱胺（20 mM）长期（45分钟）孵育后对乙酰胆碱或半胱胺的不应性会增强。提示半胱胺通过刺激内在神经元释放乙酰胆碱、作用于平滑肌毒蕈碱受体水平以及可能通过非胆碱能机制，诱导豚鼠回肠环行肌和纵行肌收缩。然而，乙酰胆碱和半胱胺诱导组织不应性的机制可能不同。
