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.
Nowak
T V
TV
Department of Medicine, Medical College of Wisconsin, Milwaukee.
Harrington
B
B
Kalbfleisch
J
J
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D007328:Insulin / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D013311:Streptozocin; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001626:Bethanechol Compounds; D007328:Insulin; D018723:Bethanechol; D013779:Tetrodotoxin; D013311:Streptozocin; D001285:Atropine; D010830:Physostigmine