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This study was performed to examine the effect of transplantation, and thus extrinsic denervation, of the small intestine on intraluminal release of serotonin and substance P. Heterotopic 40-cm-long proximal (jejunal) small intestinal isografts were performed in six 200- to 250-g adult male Lewis rats under general anesthesia. Bowel ends were exteriorized as ostomies. Six Lewis rats with neurovascularly intact 40-cm proximal small bowel Thiry-Vella loops exteriorized as ostomies served as the control animals. On the seventh postoperative day, the intestinal loops were perfused at 0.5 ml/min for three 10-min periods with normal saline followed by an equilibrium period and then for three 10-min periods with 20% dextrose. Perfusates were collected for each period and levels of serotonin and substance P were determined by radioimmunoassay. Intraluminal serotonin levels rose from 29 +/- 9 ng/ml during saline perfusion to 115 +/- 28 ng/ml during intestinal perfusion with 20% dextrose in the innervated loops and from 21 +/- 7 ng/ml to 94 +/- 26 ng/ml in the transplanted loops. While there was a statistically significant increase in mean intraluminal serotonin levels following perfusion with 20% dextrose in both the control and transplant groups, there was no difference in the intraluminal serotonin response between controls and transplant recipients. In contrast, 20% dextrose had no effect on luminal release of substance P in either group. These results indicate that extrinsic denervation of the small intestine has no effect on the intraluminal serotonin response to stimulation and suggest that serotonin and substance P are not released into the intestinal lumen by the same regulatory mechanisms.

Segmental intestinal transplantation was studied in a rat model of severe short gut syndrome across major histoincompatibility barriers. Lewis (RT1l) recipient rats whose entire small bowel (approximately 80 cm), ileocecal valve, and cecum were resected and who had no transplant, uniformly died of malabsorption on Day 9.8 +/- 0.4 (n = 11). Without cyclosporine, allograft recipients (n = 2), died of rejection on Days 8 and 10. Recipient animals with 20-cm jejunum and 40-cm jejunal transplants from Buffalo (RT1b) rats and treated daily with cyclosporine (5 mg/kg/day) intramuscularly (Days 0-28) and vitamin B12 (every other week) enjoyed significantly prolonged survival to Day 58.2 +/- 13.7, P less than 0.003, n = 10, and Day 129.1 +/- 7.4, P less than 0.001, n = 10, respectively. While 7 of 10 rats in the 20-cm jejunal transplant group died of malabsorption between Days 14 and 58, none of 10 animals in the 40-cm jejunal transplant group died of this complication. Four of 10 rats in the 40-cm jejunal transplant group thrived at 150 days after the operation, at which time they were sacrificed. Morphologically, the grafts demonstrated hypertrophic changes. The data from this study suggest that intestinal allografts have pronounced intestinal adaptative characteristics. Using segmental jejunal grafts, intestinal transplantation is an effective surgical modality for the short gut syndrome in the rat.

The cytosol of brain tissue from mature BDF1 mice contains very little dihydrofolate reductase activity but it does contain a high molecular weight nonfunctional protein which cross-reacts in a radioimmunoassay for the active enzyme. Liver cytosol contains less of this high molecular weight cross-reacting protein and more of the functional dihydrofolate reductase. The cytosol from kidney contains very little of the high molecular weight cross-reacting protein, 95% of the immunoreactive proteins being the functional form of dihydrofolate reductase. The modification of dihydrofolate reductase into a nonfunctional form may be an intrinsic property of some cells and this finding could explain the variability in measuring the activity of this enzyme in brain tissue of mature animals.