Role of Putrescine in Vitamin D-Dependent Intestinal Cell Differentiation.

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1alpha, 25-Dihydroxyvitamin D_3 (1alpha, 25(OH)_2D_3), the most potent metabolite of vitamin D_3, is now considered to be a hormone witch mediates calcium transport in the target tissues such as intestine and bone. Intestinal mucosal cells have a relatively short life span. They originate in progenitor cells present in the crypt region of the villi and differentiate and migrate toward the villus tips, where they are extruded into the lumen within 4 days. Polyamines are ubiquitous polycationic compounds of low molecular weight. The compounds are involved in cell proleration and differentiation in many cells. Three major polyamines (putrescine, spermidine, and spermine) are synthesized sequentially from ornithine. Ornithine decarboxylase (ODC) catalyzes the formation of putrescine from ornithine, a ratelimiting step in polyamine biosynthesis. Recently several reserchers have suggested the possibility that there is a conversion of the higher polyamines (spermidine and spermine) back into … More putrescine. In the present study, the effects of putrescine depletion and its supplementation on the duodenal villus length and calcium absorption were examined in chicks. Administration of either alpha-difluoro-methylornithine, a specific inhibitor of ornithine decarboxylase, or N^1,N^4-bis (2, 3-butadieny1)-1, 4-butanediamine, a specific inhibitor of polyamine oxidase, to chicks significantly decreased the duodenal content of putrescine and calcium transport activity. The putrescine depletion also induced shortening of the duodenal villus length. The inhibition of calcium absorption and villus length in the putrescine depleted chicks was almost completely restored by administering putrescine to the bird. The 1alpha, 25(OH)_2D_3 treatment increased both calcium absorption and the ATP-dependent calcium uptake by the basolateral membrane, but had no effect on the calcium uptake by the brush border membrane in the chick intestine. The duodenal basolateral membrane showed two distinct Ca^<2+>-ATPase activities : a high and low-affinity type (apparent Km for Ca^<2+> : 0.24 and 1.28muM, respectively). Treatment with 1alpha, 25-(OH)_2D_3 increased the Vmax value of the high-affinity type Ca^<2+>-ATPase without any change in the Km value. Sodium dodecyl sulfate polyacrylamide gel electrophoretic analysis revealed the formation of a calcium-dependent phosphorylated intermediate with an apparent molecular mass of 105 kD in the basolateral membrane from the intestine. These results indicate that the initial enhancement of intestinal calcium absorption induced by 1 alpha, 25(OH)_2D_3 is due to an increase in the calcium efflux mediated by the calcium pump at the basolateral membrane. In conclusion, putrescine is somehow involved in the vitamin D action in maintaining the morphological and functional development of the intestinal villus mucosa. Less