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Contractile effects of cysteamine on the guinea‐pig ileum
Author(s) -
Bakich V.,
Brown J.,
Kwok Y.N.,
McIntosh C.,
Nishimura E.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb16475.x
Subject(s) - cysteamine , acetylcholine , endocrinology , medicine , muscarinic acetylcholine receptor , hexamethonium , chemistry , tetrodotoxin , physostigmine , tonic (physiology) , myenteric plexus , stimulation , atropine , biology , receptor , immunohistochemistry
1 Cysteamine (β‐mercaptoethylamine HCl) (1.0–40.0 m M ) 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. 2 Atropine (5 μ M ) 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. 3 Tetrodotoxin increased the phasic contractions of ileal segments, but had no effect on the tonic component. 4 Treatment of MPLM preparations with morphine (1 μ M ) 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. 5 Following a response to high cysteamine concentrations (> 15 m M ) 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 μ M acetylcholine or 20 m M cysteamine) resulted in a reduced responsiveness to both. 6 A reduced sensitivity to acetylcholine or cysteamine was obtained following long‐term (45 min) incubation with acetylcholine (1 μ M ). 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 m M ) was accentuated in low Na + medium. 7 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.