Enhanced nerve-stimulated muscarinic and neurokinin contractions of ileum from streptozotocin guinea-pigs



K. J. LePard


  1. Diabetes mellitus can lead to neuropathy of enteric neurons, resulting in abnormal gut motility. These studies investigated voltage-dependent contributions of muscarinic M3 receptor activation by acetylcholine and neurokinin NK1 receptor activation by neurokinins to nerve-stimulated contractions of longitudinal ileal strips from STZ guinea-pigs, a type 1 diabetic model with insulin deficiency, but mild hyperglycaemia.
  2. Contractions to bethanechol, substance P methyl ester, and nerve stimulation were greater in diabetic as compared to control ileum.
  3. The muscarinic M3 receptor antagonist 4-DAMP at lower voltages and the neurokinin NK1 receptor antagonist SR140333 at higher voltages, but not the neurokinin NK1 receptor antagonist CP-96,345, were more effective at inhibiting nerve-stimulated immediate peak contractions and total areas of contraction of ileum from diabetic as compared to control animals. For diabetic ileum, voltage-dependent increases in the areas of nerve-stimulated contraction were observed in the presence of 4-DAMP and CP-96,345 but not SR140333.
  4. At low voltages only, nerve-stimulated release of acetylcholine was greater from diabetic as compared to control ileum.
  5. Fluorescence intensity of tachykinin-like immunoreactivity was increased in ileal myenteric ganglia from diabetic as compared to control animals.
  6. In diabetic guinea-pigs, stronger ileal nerve-stimulated contractions reflected increased release of acetylcholine at lower voltages and tachykinins at higher voltages, as well as increased sensitivity of smooth muscle M3 and NK1 receptors to acetylcholine and tachykinins. Hypoinsulinaemia may be a primary contributor to intestinal motility dysfunction in type 1 diabetes mellitus.