Carrier G O, Aronstam R S
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta.
J Pharmacol Exp Ther. 1990 Aug;254(2):445-9.
Longitudinal muscles from the ileum of rats rendered diabetic for 10 to 12 weeks by injection of streptozotocin (STZ) developed greater contractile force in response to muscarinic agonists, (acetylcholine, carbamylcholine and bethanechol) than muscles from age-matched control rats. There was no change, however, in the sensitivity of longitudinal smooth muscles to muscarinic agonists as reflected by the EC50 values for stimulation of muscle contraction. This increased responsiveness of the muscles was accompanied by a 32% reduction in the density of muscarinic receptors (381 +/- 93 vs. 560 +/- 74 fmol/mg of membrane protein) in muscles from STZ-diabetic rats. There was no change in agonist or antagonist binding affinities in muscles from diabetic rats, and there was no alteration in the distribution of receptors between the states characterized by high and low affinity agonist binding. There was also no change in acetylcholinesterase activity in muscle membranes isolated from STZ-diabetic rats. The origin of the increased responsiveness of ileal smooth muscles in this model of diabetes is not clear, but may involve changes in the muscarinic signal transduction pathway beyond the receptor level, or in the contractile apparatus itself.
通过注射链脲佐菌素（STZ）使大鼠患糖尿病10至12周后，其回肠的纵行肌对毒蕈碱激动剂（乙酰胆碱、氨甲酰胆碱和贝胆碱）产生的收缩力比年龄匹配的对照大鼠的肌肉更大。然而，纵行平滑肌对毒蕈碱激动剂的敏感性没有变化，这可通过刺激肌肉收缩的EC50值反映出来。肌肉反应性的这种增加伴随着STZ糖尿病大鼠肌肉中毒蕈碱受体密度降低32%（381±93对560±74 fmol/mg膜蛋白）。糖尿病大鼠肌肉中激动剂或拮抗剂的结合亲和力没有变化，并且在以高亲和力和低亲和力激动剂结合为特征的状态之间，受体的分布也没有改变。从STZ糖尿病大鼠分离的肌肉膜中的乙酰胆碱酯酶活性也没有变化。在这种糖尿病模型中，回肠平滑肌反应性增加的原因尚不清楚，但可能涉及毒蕈碱信号转导途径在受体水平之外的变化，或者收缩装置本身的变化。
