AJP - Gastrointestinal and Liver Physiology

Fukuda, S; Kopple, JD

doi: N/Apmid: N/A

Net production or utilization (Qmet) of histidine by the kidney was evaluation or utilization (Qmet) of histidine by the kidney was evaluated in 11 normal and 8 chronically uremic female dogs during intravenous infusion, first of half-normal saline and then an amino acid solution containing L-histidine. Also, Qmet for histidine, alanine, beta-alanine, and carnosine (beta-alanyl-L-histidine) was determined during infusion of half-normal saline and then carnosine into the renal artery in seven normal dogs. During infusion of half-normal saline, Qmet histidine, calculated from the plasma data, was significantly positive in normal but not uremic dogs. Qmet histidine correlated with creatinine clearance. In uremic dogs, plasma histidine was decreased possibly due to decreased renal production and increased urinary excretion. Qmet histidine, calculated from the whole blood data during infusion of half-normal saline, was positive but not significantly so. During carnosine infusion, there was significant utilization of carnosine, and histidine production increased. Thus during fasting, the dog kidney appears to produce histidine, and histidine production increases with carnosine infusion. Hydrolysis of carnosine, possibly by carnosinase, may be a source of histidine released by the dog kidney.

Bueno, L; Ruckebusch, Y

doi: N/Apmid: N/A

Both slow waves and bursts of spike potentials were recorded prior to birth in dogs and sheep. At 0l7-0.8 of term the slow-wave frequency of the jejunum did not exceed 12/min. It increased in a similar way during the last stage of fetal life in sheep and after birth in dogs. Adult values were attained 10-15 days after birth in the lamb but only by 40 days of age in the puppy. In both species, three stages of development of the spiking activity were identified. Stage 1, termed unorganized spiking activity, was converted in the fetal lamb at 0.8 of term to a fetal pattern (stage 2) characterized by cyclic 3- to 4-min periods of regular spiking occurring at 10- to 20-min intervals and propagated along a short intestinal segment. Stage 3, which corresponds to myoelectric complexes, occurred during the last 10 days of fetal life. In dogs, the fetal pattern (stage 2) was recorded from 5 days before to 15 days after birth. Stage 3 was seen in the 15-day-old neonate. The results suggest that the patterns of electrical activity seen in the last third of fetal life can be related to their function of mixing and absorbing but not expelling intestinal contents. They indicate that the electrical phenomena of the gastrointestinal tract are in accord with the overall greater maturity and independence of the newborn sheep compared to the dog.

Baum, D; Griepp, R; Porte, D

doi: N/Apmid: N/A

Glucose-induced insulin release was studied in young dogs during acute and chronic hypoxia, alone and in combination. Six experimental animals were rendered chronically hypoxic (PaO2, 43.4 +/- 0.5 torr) by creation of a right-to-left shunt at age 6-8 wk. Six control animals underwent sham procedures (PaO2, 85 +/- 2.2 torr) at the same age. During air breathing, glucose-induced plasma insulin increases were similar in chronically hypoxic and control animals. When severe hypoxia was acutely produced by ventilation with low-oxygen mixtures in experimental (PaO2, 23.7 +/- 1.7 torr) and control animals (PaO2, 26.3 +/- 1.0 torr), plasma insulin responses were markedly inhibited in both. On the other hand, acutely lowering oxygen tensions of control animals (PaO2, 37.5 +/- 1.4 torr) to levels close to those of air-breathing chronically hypoxic animals did not affect the insulin responses. These observations suggest that glucose-induced insulin release is inhibited by acute severe hypoxia despite previous chronic oxygen deficiency. In contrast, moderate hypoxia, acute or chronic, does not appear to affect the insulin response to a glucose load.

Kreulen, DL; Szurszewski, JH

doi: N/Apmid: N/A

In vitro preparations consisted of the right and left celiac, superior mesenteric and inferior mesenteric ganglia with attached extrinsic nerves, vasculature, mesentery, and colon. There were no systematic differences in membrane electrical properties (recorded intracellularly) between neurons in the different ganglia. Stimulation of associated nerve trunks produced graded synaptic responses in plexus neurons. Presynaptic fibers were found in splanchnic and mesenteric nerves. Input from celiac nerves dominated in the celiac galglia; input from the intermesenteric fibers dominated in the superior mesenteric ganglion. When the ganglia were attached to the entire colon, 33% of the neurons in the celiac and 54% in the superior mesenteric ganglion received a continuous excitatory synaptic input that was increased by distending the colon. This input was interrupted irreversibly by transsection of the mesenteric nerves. These results show that both the afferent and efferent pathways of a peripheral reflex arc are located in the mesenteric nerves and may mediate visceral reflexes between mechanoreceptors and sympathetic neurons in the colon.

Dinda, PK; Hurst, RO; Beck, IT

doi: N/Apmid: N/A

This study was undertaken to investigate the effect of alcohol on the activity of jejunal disaccharidases (DS). The activity of DS in a preparation of purified brush border membrane of hamster jejunum was measured in the absence and in the presence (0.8 to 6.4% wt/vol) of ethanol. To compare the effect of alcohol on DS with its action on a brush border enzyme of a different group, we also measured the activity of alkaline phosphatase (AP) under similar conditions. Ethanol depressed the activity of sucrase, maltase, and lactase in a dose-dependent and time-dependent manner, but it stimulated the activity of AP. The ethanol-induced inhibition of DS was completely reversible. Kinetic studies indicate that ethanol depressed the Vmax and increased the Km of sucrase and lactase. The Vmax of maltase also decreased, but the Km of this hydrolase was not affected by ethanol. From the results of this study it would appear that acute exposure of the jejunal brush border to ethanol depresses the DS activity of the membrane and that (because the AP was not depressed) the ethanol-induced inhibition of DS is not the result of a general inhibition of all enzymes of the brush border.

Witters, LA; Trasko, CS

doi: N/Apmid: N/A

The roles of glucagon and insulin in the direct short-term regulation of hepatic free fatty acid (FFA) metabolism were studied in hepatocytes isolated from fed, fasted, and streptozotocin-induced diabetic rats. In fed animals, the principal metabolic product of palmitate metabolism was triglyceride, whereas ketones were the major product in fasted and diabetic animals. Glucagon at physiological concentrations increased ketogenesis and decreased triglyceride synthesis from palmitate in hepatocytes from fed rats at FFA concentrations 1.0 mM or less. Insulin had no effect on FFA metabolism when present as the sole hormone, but could antagonize the actions of submaximal concentrations of glucagon. The metabolism of palmitate in fasted or diabetic hepatocytes was unaffected by either hormone. Ketogenesis from octanoate was also unaffected by hormone addition in all cell types. These data are consistent with a locus of hormonal regulation at a step prior to beta-oxidation of fatty acid. Glucagon and insulin may modulate FFA metabolism by both intrahepatic and extrahepatic mechanisms.

McKinley, MJ; Denton, DA; Hatzikostas, S; Weisinger, RS

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Intravenous infusion of angiotensin II over the dose range 3-20 microgram/h for 15 min caused a dose-dependent reduction in parotid saliva secretion and increase in arterial blood pressure in conscious sheep. The blood levels of angiotensin II contrived by these infusions were probably within the physiological range for sheep. Infusion of angiotensin II (3 microgram/h) into the carotid artery ipsilateral to the parotid gland under study caused greater reduction in saliva secretion rate than an equivalent infusion of angiotensin II into the contralateral carotid artery. This result suggests a direct effect of angiotensin II at the parotid, possibly by a constrictor action on its vasculature or by altering water and electrolyte transport by the gland. In sodium-deplete sheep, intravenous infusion of the angiotensin antagonist saralasin (1 mg/h for 1 h) caused transient increase of saliva flow for 20-30 min. It is suggested that angiotensin II may have a physiological role in regulating parotid saliva secretion during sodium depletion.

Bybee, DE; Brown, FC; Georges, LP; Castell, DO; McGuigan, JE

doi: N/Apmid: N/A

The effect of somatostatin (GH-RIH) infusion (2 microgram/min) on lower esophageal sphincter pressure (LESP) responses to various stimuli was evaluated in adult male baboons. GH-RIH infusion did not affect basal LESP, but did cause a significant suppression of mean immunoreactive insulin (IRI) to 5.8% of basal values (P less than 0.05). Pentagastrin IV caused dose-related increases in LESP that were unaffected by GH-RIH. Abdominal compression caused a threefold rise in LESP (P less than 0.005) both without and with GH-RIH. However, atropine (20 microgram/kg iv bolus) completely blocked this cholinergic LES pressure response. Intragastric alkali as well as intragastric glycine caused significant increases in LESP (P less than 0.05). These LESP responses to alkali and to glycine were totally abolished by GH-RIH. In conclusion, GH-RIH infusion in the baboon does not affect basal LESP, LES smooth muscle response to exogenous stimulation, nor a cholinergically mediated LES response. GH-RIH does inhibit the response of LESP both to intragastric alkali and to glycine by the apparent suppression of a hormonally mediated mechanism.

Lichtenberger, LM; Trier, JS

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Gastrointestinal epithelial cell proliferation is stimulated during lactation in the rat. Serum gastrin levels and food intake are also increased during lactation. We investigated the role of gastrin and food intake as possible mediators of duodenal mucosal growth during the first 15 days of lactation. As the lactation period progressed, significant increases in the following crypt properties were noted: 1) crypt length; 2) cells/crypt; 3) labeling index; and 4) dimensions of the proliferative zone. Maternal serum gastrin levels rose abruptly by the first day of birth and remained elevated throughout lactation. The increases in crypt cell proliferation significantly correlated with food intake but not with serum gastrin levels during lactation. Mucosal mass and villus-crypt dimensions were also significantly increased above virgin levels in lactating antrectomized rats. These results suggest that the increase in duodenal growth during lactation most probably is not mediated by postpartum hypergastrinemia and that the increase in cell proliferation may be a direct response to an enhancement in food intake.

Bhattacharyya, AK; Goodpasture, JC; Zaneveld, LJ

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Mouse spermatozoa possess a neutral proteinase, acrosin, that is to a large extent (70-80%) present in the zymogen (proacrosin) form. Acid extraction yields higher amounts of acrosin than detergent extraction. Synthetic inhibitor studies indicate that mouse acrosin has a serine and histidine at its active site and hydrolyzes the peptide bonds of lysine and arginine but of not phenylalanine. An inhibitor of acrosin is associated with mouse spermatozoa, capable of preventing the activity of at least 60% of all available acrosin. Acrosin activity is essential for fertilization because natural and synthetic inhibitors of mouse acrosin prevent the union of the gametes. Also, the relative inhibitory activity of synthetic agents toward acrosin runs approximately parallel to their antifertility activity. The percent of acrosin in the proacrosin form does not change after capacitating mouse spermatozoa in vitro.