ABSTRACT. Previous studies have suggested similarities between the effects of exogenously administered glucocorticoids and prostaglandins in the developing rat small intestine. In this study the effects of exogenously administered glucocorticoids and prostaglandins were compared. In addition, the effects of prostaglandins in adrenalectomized rats were evaluated. Members of both classes of compounds stimulate small intestinal disaccharidase activities, and increase RNA to DNA ratio and brush border membrane protein synthesis. Hydrocortisone accelerates enterocyte turnover, whereas prostacyclin does not. Enteral administration of 16,16-dimethyl prostaglandinEz stimulates disaccharidase activities in intact as well as shamoperated and adrenalectomized animals. The data suggest that certain prostaglandins may play a role in small intestinal metabolism which is similar to that of the glucocorticoids but is independent of the adrenal-intestinal axis. Glucocorticoids are known to play a significant role in the development of small intestinal biochemical function. These hormones appear to mediate a series of enzymatic changes in the small intestine of rats during the 3rd wk of postnatal life (I-3). Administration of hydrocortisone or ACTH during the 2nd postnatal wk causes precocious appearance of sucrase activity (4), whereas adrenalectomy at this time markedly slows the usual increase of sucrase activity (5). In adult rats, sucrase activity is independent of glucocorticoids (6).In a previous study by our group (7), prostaglandins were administered to suckling rats to determine their effects on growth and development. Analysis of small intestinal hydrolase activities demonstrated effects similar to those of the glucocorticoids. Other than this, little information is available regarding the physiological role of prostaglandins in the gastrointestinal tract of the developing fetus and neonate. More recent studies by Koelz (q a/. (8) have demonstrated that an enterally administered prostaglandin analog, 16,l 6-DMPGE2, will stimulate disaccharidase activity in the small intestine of suckling but not adult rats.Since the stimulation of the enzyme activities by the glucocorticoids and prostaglandins are similar in many respects, we decided to investigate further the comparative effects of these two classes of compounds. The purpose of these studies was
Since pancreatic amylase (PA) i s absent in prematures, GP hyd r o l y s i s depends on a l t e r n a t e enzymes. To assess premature SA a s a PA surrogate we evaluated i t s production, acid r e s i s t a n c e and hydrolytic potency in a simulated oro-pharyngeal (OP), g a s t r i c ( 6 ) and i n t e s t i n a l ( I ) environment. SA was added tp4yield 1.1 u/ml of a "modular" formula containing 7 gm/dl of C GP with degrees of polymerization (DP) 18-29 glucose u n i t s . After an 0.25 min. OP phase the G-phase was i n i t i a t e d by d i l u t i o n with pepsin/HCl t o y i e l d pHs of 2, 3, 4, o r 5. After 5 min. o r 3 hours pH was adjusted t o 7.0 with cholate/trypsin chymotrypsin/Na CO ( I phase). After t h e OP-and G-phases and 15, 60 and 180 ~n ? n .~o f I-phase, oligosaccharides were separated by t h i n l a y e r chromatography. % breakdown=cpm i n DP 1-9 / cpm i n t o t a l sample x 100. Results: In 11 prematures SA a c t i v i t y was 1-33 u/ml; isozyme prof i l e d acid r e s i s t a n c e were i d e n t i c a l t o a d u l t SA. Substantial G-phase breakdown only occurred with 3 hour exposure a t pH 4 (12%) and 5 (32%). In t h e I-phase SA a c t i v i t y resumed. Prior Gphase pH a f f e c t s ultimate I-phase breakdown, p<.O01. (After 5 min. G-phase a t pH 2&5, I-phase breakdown = 8&25%; a f t e r 3 hour G-phase a t pH 2&5, I-phase = 17&55%.) Conclusion: The limited SA of premature s a l i v a can produce s i g n i f i c a n t GP digestion in both t h e stomach and small i n t e s t i n e . DEVELOPMENT OF GLUTAMINASE RU3ffi THE VILLUS-CRYPT AXIS OF RAT JFJUNUM. L.E. Nagy and N.' 704 Kretchmer. University of California,Berkeley, ~e p a r m ~u t r i t i o n a l Sciences.During the developnent of i n t e s t i n a l c e l l s , energy is required f o r a number of functions: mintenance of c e l l u l a r p r o l i f e r a t i o n , d i f f e r e n t i a t i o n and migration, and absorption and packaging of absorbed material. While glutamine is the m j o r f u e l source f o r the e n t i r e s m l l i n t e s t i n e , t h e u t i l i z a t i o n of glutamine during the development of the i n t e s t i n a l c e l l has not been described. W e have examined t h e regulation of glutaminase (EC 3.5.1.2), the e n t r y enzyme f o r glutamine metabolism, i n enterocytes i s o l a t e d along t h e villus-crypt a x i s from jejunum. S p e c i f i c a c t i v i t y of glutaminase, vrnol/mg protein/h, was 5.07r0.60 i n v i l l u s c e l l s (0-758 of the t o t a l p r o t e i n removed from jejunum), 6.07r1.29 i n the v i l l u s c r y p t junction c e l l s (75-958 of t o t a l p r o t e i n ) and 3.91 r0.80 i n c r y p t c e l l s (95-1008 of t o t a l p r o t e i n ) . Quantity of glutaminase p r o t e i n was determined by a d o t inmunobinding a s s a y using an antibody t o p u r i f i e d glutaminase.Imunoreac t i v e glutaminase-protein r e l a t i v e t o t o t a l c e l l p r o t e i n was 6.03r1.99 c p / ~g homogenate p r o t e i n i n v i l l u s c e l l s , 3.34fl.16 cpn/vg a t the villus-cryp...
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