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Gastro-Intestinal Tract Function in Sheep Infused with Somatostatin

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Gastro-Intestinal Tract Function in Sheep Infused with Somatostatin Aust. 1. BioI. Sci., 1985, 38, 393-403 Gastro-intestinal Tract Function in Sheep Infused with Somatostatin T. N. Barry, A,B G. J. Faichney, A and Carolyn Redekoppc A Division of Animal Production, CSIRO, P.O. Box 239, Blacktown, N.S.W. 2148. B On leave from: Invermay Research Centre, Mosgiel, New Zealand. Present address: Department of Animal Science, Massey University, Palmerston North, New Zealand. C Department of Endocrinology, Princess Margaret Hospital, Christchurch, New Zealand. Abstract The effect of a 5-day continuous intravenous infusion of somatostatin (4·6 ng min- I kg-I) was studied, using anoestrous ewes given 791 g dry matter per day of a 60: 40 lucerne hay: oat grain pelleted diet from a continuously moving belt. 5ICr-EDTA, I03Ru-phenanthroline and lignin were used as markers to determine digesta mean retention times (MRT) by a continuous infusion-total sampling procedure. The somatostatin infusion increased the concentration of somatostatin in venous plasma within the physiological range from 10 to 76 ng/I, decreased plasma concentrations of prolactin and thyroxine, but had no effect upon plasma concentrations of insulin and glucagon. It had no effect upon digesta-free weight of the rumen and omasum but consistently decreased the weight of all post-ruminal segments of the gastro­ intestinal (GI) tract. The infusion increased the accumulation of digesta in the abomasum and caecum. Total MRT of all three markers in the entire GI tract was unaffected by somatostatin infusion, but the proportion of total MRT spent in the abomasum + small intestine + caecum increased and the proportion spent in the large intestine and rumen decreased. Somatostatin infusion decreased apparent endogenous abomasal secretion, increased water flow from the rumen and into the abomasum and decreased voluntary water consumption. It is proposed that the prime site of somatostatin action was in the abomasal to caecal region, where somatostatin-secreting D cells are found in greatest concentration, that effects observed in the large intestine and rumen may represent secondary compensatory mechanisms and that the effects observed were due to direct action of somatostatin and were not mediated by other GI hormones. Introduction The tetradecapeptide somatostatin (mol. wt 1639·9) was first detected in ovine hypothalamic tissue as a factor which inhibited growth hormone secretion from the pituitary gland (Brazeau et al. 1973). Subsequently, somatostatin has been detected in the pancreatic tissue of a number of mammalian species; it has been suggested that it inhibits insulin and glucagon release from the pancreas and modifies the extraction of these hormones by the liver (Vale et al. 1975; Brockman 1979; Ishida et al. 1980). Schusdziarra (1979) observed that intravenous somatostatin infusion in dogs reduced plasma triglyceride concentrations following a meal, and proposed that the release of somatostatin from the gut may be involved in the homeostatic regulation of the rate of nutrient absorption. In growing sheep, Barry et al. (1982) found that abomasal infusion of casein decreased plasma somatostatin concentration, suggesting the possibility that somatostatin could be involved in the regulation of absorption rate in this species too. The objective of the present experiment was to study the effect of a continuous 0004-9417/85/040393$02.00 394 T. N. Barry et al. intravenous infusion of somatostatin on the rate of passage of indigestible markers through the gastro-intestinal (GIl tract of sheep, on net water exchanges along the tract, on the weights of individual segments of the GI tract and on endocrine status. Materials and Methods Animals Two groups of five anoestrous Corriedale ewes aged 5-6 years were used; the mean liveweights (± s.e.) of, respectively, the control and treatment groups were 38·4 ± 0·94 and 40·0 ± 2·61. The ewes were shorn 57-58 days prior to slaughter. They were held in individual pens for 4 weeks and were then transferred to metabolism cages in a room with normal windows but with continuous artificial lighting. The mean maximum and minimum temperatures in the room were 22·2 ± O·loC and 19·6 ± 0·2°C. Diet The diet was a ground and pelleted mixture of 60% lucerne hay and 40% oat grain. On a dry matter (DM) basis, the mean composition (glkg) of the diet was: nitrogen 22·8, cell wall organic matter 417, acid­ detergent fibre 292, acid-detergent lignin 71, crude fat 40 and ash 59. It was given daily at the rate of 791 g DM from the day of shearing and during the 4 weeks prior to slaughter it was presented continuously from a conveyor belt. Voluntary water intake was measured daily, and corrected for evaporation losses. Total water intake included that consumed in the pellets. Experimental Methods Measurements were made first on the control then on the treatment group. In each period, 3 weeks before slaughter, each sheep was fitted with a self-retaining rumen catheter (Faichney and Colebrook 1979). In the second period, a polyvinyl catheter (I ·5 mm o.d., I· 0 mm i.d.; Dural Plastics and Engineering, Dural, N.S.W.) was placed in a jugular vein of each sheep I day prior to the commencement of a somatostatin infusion. The catheter was filled with sterile saline containing 200 i.u. heparin/m!. During each period, faecal output was collected for 7 days prior to slaughter and the markers were infused into the rumen for at least 5 days and, in the second period, the intravenous somatostatin infusion was maintained simultaneously for at least 5 days; all infusions were terminated at slaughter. Urine output was collected during the 24 h prior to slaughter. Infusion procedures The markers used were the 51Cr complex of EDTA (51 Cr-EDTA) (Downes and McDonald 1964) and 103Ru-Iabelled tris-(l,I 0-phenanthroline)-ruthenium(II)chloride(103Ru-phen) (Tan et al. 1971). The infusate was made up to contain 37 kBq 51Cr and 7·4 kBq 103Ru per millilitre, with 5·4 /Lg inert Cr-EDTAIkBq 51Cr added as carrier. Following a priming dose of 30 ml into the rumen, the infusion was begun and maintained at 47 mllday for at least 5 days before slaughter. Synthetic cyclic somatostatin (mol. wt 1639·9; Sigma Chemical Co., Missouri, U.S.A.) was dissolved in sterile saline (9 g NaCIII) containing bovine serum albumin (2·5 gil) to act as carrier and to prevent possible binding of somatostatin to glassware and tubing. Both somatostatin concentration in the infusate and the pumping rate were adjusted for each sheep such that the somatostatin infusion rate was constant at 4·6 ng min - 1 kg - 1 liveweight. Mean somatostatin concentration in the infusate was 2083 /LgIl and the mean infusion rate was 5·35 mllh. The infusion was maintained for at least 5 days. The infusates were stored at 4°C for up to 3 days before use, and were kept on ice whilst being infused. Sampling procedures A composite sample of faeces was prepared for each sheep by combining 20% of the daily output; this and a urine sample were stored at - IO°C. Blood samples were drawn into heparinized syringes by jugular venipuncture of all animals at 10·00 h for 3 consecutive days; the blood was transferred to tubes kept in an ice slurry and 0·33 ml aliquots of plasma prepared by centrifugation were pooled each day to give I-ml samples for individual hormone analyses. The proteinase inhibitor Trasylol (Bayer, Leverkusen, W. Germany) was added to those tubes (1000 ki.u.lml plasma) that were to be assayed for somatostatin, glucagon and gastrin, to prevent proteolysis of these hormones. In somatostatin-infused sheep, the blood samples were taken after the infusion of somatostatin and the indigestible markers had been running for 48, 72 and 96 h, and after the markers had been infused for corresponding times in control sheep. Somatostatin and Gut Function in Sheep 395 The animals were killed by the intravenous administration of concentrated sodium pentobarbitone, after which the abdomen was opened and the oesophagus, the omasal-abomasal junction and the abomasal­ duodenal junction were quickly ligated and the entire GI tract removed. The small intestine was then divided into five approximately equal sections and the large intestine into the caecum-proximal colon (caecum), the centripetal (spiral colon I), centrifugal (spiral-colon 2) and terminal colon and the rectum. Total digesta in each segment was removed and weighed and subsamples taken for the determination of radioactivity, dry matter and lignin. Visible fat was then trimmed from all gut tissues, which were then washed, blotted dry and weighed. The reticulo-rumen will be referred to in this paper as the rumen. Analyses Samples of digesta, faeces and urine were assayed for SICr and J03Ru simultaneously in duplicate tared vials using a model 5320 Auto Gamma Spectrometer (Packard Instrument Co., Illinois). Hormones were determined by the standard radioimmunoassay procedures described by Barry et al. (1982). Total glucagon was measured using antibody K4023, which recognizes both pancreatic glucagon and enteroglucagon; pancreatic glucagon was also measured with a specific antibody and enteroglucagon estimated by difference. Gastrin was determined as described by Reynolds et al. (1984) and thyroid stimulating hormone as described by Hopkins et al. (1975). The interassay variation and assay detection limits for the hormone assays were: growth hormone 8 '6%, 1·2 ",gil; prolactin 7·4%,2·4 ",gil; somatostatin 14,6%, 7·0 ng/I; insulin 4 ·0%, 1· 5 mi.u.l1; glucagon 6·3%, 15·3 ngll; gastrin 10%, I· 3 pmolll; thyroid stimulating hormone 13·8%, 0·5 ",gil; thyroxine 6%, 2·0 nmolll; tri-iodothyronine 6%, 0·04 nmolli. Plasma glucose was determined using glucose oxidase (frinder 1969) and plasma non-esterified fatty acids (NEFA) were determined as described by Patterson (1963).
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