Adaptation of cholinergic enteric neuromuscular transmission in diabetic rat small intestine

Representative longitudinal muscle strips (6 x 10 mm) from distal small intestine were obtained from rats after 1, 2, and 3 mo of streptozocin-induced diabetes. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (1-ms pulse duration, 30-270 mA, 10 Hz) in the presence of Krebs solution and Krebs solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in all strips. After 1 mo, significant differences in the amplitudes of the atropine-sensitive contractions were found between the diabetic rats and nondiabetic controls. Insulin-treated diabetic rats showed contraction responses that were intermediate in amplitude. After 2 mo, the difference between the control and diabetic groups was less evident but still significant. After 3 mo, the previously noted difference in the atropine-sensitive contractions between the diabetic and control groups had resolved. No significant differences among the three groups were noted in the amplitudes of the atropine-resistant contractions. Field stimulation delivered at pulse durations of 50 ms in the presence of neural blockade with tetrodotoxin (5 x 10(-6) M) produced similar contraction amplitudes among the three groups at any respective time phase of the study. Dose-response studies of intestinal muscle after 3 mo of untreated diabetes showed normal tension development to both bethanechol chloride and physostigmine. These results indicate that streptozocin-induced diabetes is acutely associated with defective cholinergic neuromuscular transmission in the myenteric plexus of the distal small intestine. The abnormality is less evident after 2 mo of untreated diabetes and resolves spontaneously after 3 mo. Insulin treatment appears to accelerate this resolution.