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D S Parsons

Publications and source records attributed to D S Parsons.

At least 91 records · Page 5Linked to original sources

Use of high performance liquid chromatography to study absorption and metabolism of purines by rat jejunum in vitro.

A simple and specific analytical method incorporating high performance (anion-exchange) liquid chromatography has been used to study the absorption and metabolism of some purine derivatives in an in vitro preparation of adult rat jejunum. When present in the lumen the purine bases guanine (4 X 10(-5)M), hypoxanthine or xanthine (10(-4)-3 X 10(-4)M) do not appear in the serosal secretions but the uric acid (UA) content of these secretions is increased. With UA in the intestinal lumen (10(-4)-3 X 10(-4)M) the serosal UA is increased, in some cases to a higher concentration than that in the lumen. With adenine in the lumen (10(-4)-10(-3)M) there is an increased appearance of UA and adenine also appears in the serosal secretions, but the concentration of adenine never exceeds that in the lumen. It is concluded that purines absorbed from the lumen are significantly metabolized to UA during translocation across rat jejunum. Negligible amounts of metabolites are found in the luminal solutions except for guanine which appears to be degraded in the lumen.

Absorption↗

Role of anions and carbonic anhydrase in epithelia.

The existence of carbonic anhydrase (carbonate dehydratase, EC 4.2.1.1) in blood was suspected and sought because the rates of spontaneous hydration and dehydration of CO2 and carbonic acid were slow compared with the rates of exchange of CO2 with blood. The existence of the enzyme in absorbing and secreting epithelial tissues has, in contrast, often been sought because its presence was required for the operations of theoretical models for the movements of H+ ions or HCO-3 into or out of epithelial cells. In addition to the HCl-secreting gastric mucosal epithelium, the enzyme was subsequently found in the rumen, in the kidney, especially those of species that produce acid urine, and salivary gland, the liver and biliary duct system, the mucosa of the small intestine, caecum and colon, the choroid plexuses and ciliary body of mammals, in toad urinary bladder and in the Cl-secreting cells of fish gill. The presence of carbonic anhydrase in exocrine pancreas does not seem to be well established. The enzyme, of molecular mass about 30kDa and containing one zinc atom, exists in three related forms: one of high specific activity and two of low specific activity, one of which is found in red skeletal muscle. Although most, but not all, types of erythrocyte contain both varieties, epithelia usually contain only the high-activity enzyme; however, ox rumen contains large quantities of the low-activity variety as do guinea-pig caecal and colonic mucosae. Salt transport in the intestinal tract is associated with movements of HCO-3 and H+ ions, yet although carbon dioxide stimulates solute and fluid transport in the gall bladder in jejunum, and inhibitors of carbonic anhydrase reduce fluid and ion transport across many epithelia the role of the enzyme in epithelial transport is not clearly understood. Knowledge of the rates of hydration and dehydration of CO2/HCO-3 in the fraction of the tissue water responsible for the H+-HCO-3 movements in many secretory epithelia is currently lacking.

Animals↗

Sodium movements across the vascularly perfused anuran small intestine and colon.

Values of unidirectional Na fluxes measured across the vascularly perfused small intestine of three anuran species are higher than those found in other preparations in vitro. In Rana ridibunda and R. pipiens no net movement of Na across the small intestine can be detected. In contrast, the unidirectional fluxes of Na across the colon of R. ridibunda and R. pipiens are lower than across the small intestine and a significant net absorption is found. Apparent loading and unloading pools for Na within the small intestine, as measured with tracer Na under standard experimental conditions, consist largely of extracellular Na presumably within the bulk phase of the lumen. The size of these pools can be greatly reduced by the rapid addition to or removal from the lumen of tracer. The loading pool appears to occupy not more than about 9% of the total tissue water, equivalent to about 20% of the extracellular water of the tissue. The washout of tracer Na from preloaded small intestine into the vascular bed is bi-exponential and appears from a pool, or pools, of apparent greater size than that of the loading pool. The results show that Na can move very rapidly across the small intestine and suggest that a high proportion of this movement occurs possibly via paracellular shunt pathways.

Animals↗

Influence of vascular and lumen flow on sodium movements across anuran intestine in vitro.

There is a positive linear relation between the vascular flow rate and the magnitudes of the unidirectional fluxes of Na in either direction in the steady state across the small intestine of the frog. Both unidirectional Na fluxes increase to the same extent with an increase in vascular flow so there is no apparent effect of flow on net Na movement. Raising the vascular flow rate in individual experiments increases the lumen-blood Na flux proportionately, but reducing the flow from an initially high value reduces the lumen-blood flux only slowly at first then more rapidly. The unidirectional Na fluxes increase linearly as the lumen flow rate is increased. In the colon increasing the vascular flow rate also increases the lumen-blood Na flux but changing the vascular flow rate has little effect on the blood-lumen flux, the net absorption of Na is invariably increased as the vascular flow increases. Using 14C-labelled sucrose as a marker for the extracellular space of the small intestine, it can be shown that the increases in Na flux found with increased vascular flow rates are associated with an increase in this sucrose space. An increase in sucrose space, therefore, seems to enhance the accessibility of the low resistance, paracellular pathways for Na to and from the blood across the epithelium.

Animals↗

The Sabinas syndrome.

We have defined a new autosomal recessive disorder in patients stemming from a small community in northern Mexico. Diagnosable at birth, its major symptoms include brittle hair, mental retardation, and nail dysplasia. Structural hair abnormalities are seen by both light and electron microscopy. Hair cystine content is reduced while the copper/zinc ratio in hair is increased.

Adolescent↗

Naloxone and shuttlebox self-stimulation in the rat.

Rats self timed electrical brain stimulation on and off periods in a shuttlebox. Electrodes for self-stimulation were located either in the lateral hypothalamic area (LHA) or the periaqueductal gray (PAG). Doses of the narcotic antagonist, naloxone, were administered intraperitoneally immediately prior to self-stimulation testing. Doses of 1.0, 5.0, 10.0 or 50.0 mg/kg failed to alter shuttlebox self-stimulation behavior. These results are inconsistent with one lever-press self-stimulation study employing PAG electrodes [3], but agree with other studies using LHA electrodes [9, 15, 21, 24). Possible reasons for the discrepancy are suggested.

Animals↗

Influence of vascular flow on amino acid transport across frog small intestine.

1. The vascularly perfused intestine of the frogs, Rana ridibunda and R. pipiens, was used to investigate the transfer of the non-metabolized amono acids alpha-amino isobutyric acid (AIB) and 1-amino-cyclopentane-1-carboxylic acid (cycloleucine) across the intestinal epithelium from the lumen into the portal vein. 2. The steady-state rate of transfer of cycloleucine was significantly increased with increasing vascular flow rate, both in the presence and absence of Na in the fluid in the intestinal lumen, although at all flow rates the transfer was lower when the Na was replaced by K. The relatively high rate of transfer of cycloleucine seen at high rates of vascular flow when the luminal perfusate was free of Na was almost abolished when leucine was added to the lumen. 3. When the vascular flow is interrupted cycloleucine is taken up from the lumen and accumulates in the tissue. The accumulated amino acid can be measured during the subsequent wash-out when the vascular flow is resumed. The rates of transfer of accumulated cycloleucine as measured during subsequent wash-out were lower than those found at continuous flow; it is suggested that there is a limit to the amount of amino acid that the epithelial tissue can retain when the vascular flow is interrupted. A significant accumulation of cycloleucine occurs when Na is present in the lumen, but the accumulation is negligible when Na is replaced by K. 4. The unloading of the amino acids AIB and cycloleucine from the epithelium into the vasculature was investigated. The two amino acids showed markedly different kinetics of exit, that of AIB being monoexponential while that of cycloleucine was biexponential. Moreover, the rate of exit of cycloleucine was influenced by the presence of Na in the intestinal lumen, and by the rate of vascular perfusion. The apparent diffusion coefficients for the exit were smaller than those expected had unloading taken place by unobstructed free diffusion. 5. It is concluded that specific processes for exit from the epithelium play a significant role in amino acid transfer across the small intestine, and that the exit of AIB is more restricted than that of cycloleucine.

Amino Acids↗

Movements of monosaccharides between blood and tissues of vascularly perfused small intestine.

1. A method involving the analysis of pulse transients of the vascular concentrations of test sugar and extracellular marker has been used to study the movements of non-metabolized sugars between the cells and vascular fluid of the vascularly perfused small intestine of R. ridibunda. Reasons are given for supposing that the method does properly measure the net entry of sugars into a cellular compartment that includes at least the epithelium. 2. It is found that while the glucose analogues, 3-O-methyl-D-glucose (3MG) and 2-deoxy-D-glucose (2)DG) are able to enter a cellular compartment when they are added to the vascular bed, alpha-methyl-D-glucoside (alpha MG) is able to enter the compartment only at a very slow rate from the vascular bed. In contrast, 3MG and alaph MG are well absorbed from the lumen whereas the inward permeability of 2DG across the lumen face of the epithelium is very low and, unlike 3MG and alpha MG, is not influenced by the presence in the lumen of other transported sugars. 3. The presence of phlorizin in the intestinal lumen increases the flux of alpha MG and of 3MG in the direction vascular bed--bulk phase of lumen. Reasons are given for supposing that the movement of sugars from the vascular bed into the lumen may involve a cellular route but occurs, at least in part, through a paracellular, extracellular route. 4. The exit of monosaccharides that have been loaded previously into the epithelium either from the lumen or from the vascular bed has been investigated. 3MG washes out rapidly into the vascular bed and the exit is stimulated by the addition of D-glucose to the intestinal lumen and by the addition of 2DG, but not alpha MG, to the arterial infusate. In contrast, alpha MG, loaded into the epithelium from the lumen, washes out of the cells only slowly into the vascular bed, so that even with high rates of vascular perfusion alpha MG accumulates within the tissue. The sustained accumulation of alpha MG implies that not only is the permeability for exit into the blood restricted for this sugar, but also the permeability is low across the brush border in an outward direction, cell to lumen ('lobster pot effect'). The wash-out of 3MG into the vascular effluent is sufficently rapid that only in the absence of vascular perfusion is 3MG accumulated within the tissue. 5. The contrasting properties of the monosaccharide transport systems accessible from the intestinal lumen and the vascular bed respectively are discussed in relation to the problems of epithelial transport of monosaccharide.

Animals↗

Effects of vascular perfusion on the accumulation, distribution and transfer of 3-O-methyl-D-glucose within and across the small intestine.

1. Factors affecting the transfer of the non-metabolized, ;actively transported' sugar, 3-O-methyl-D-glucose (3MG) across the small intestinal epithelium have been examined in vascularly perfused anuran intestine. Transfer has been studied during absorption in the steady state, and also during the period of transition from one steady state to another.2. During the steady state, the rate of absorption of 3MG from the intestinal lumen is equal to the rate of appearance in the portal venous effluent; this rate of transfer is to a small, but significant, extent directly related to the rate of arterial perfusion. With phlorizin in the intestinal lumen, transfer across the epithelium is reduced to very low rates which are independent of the rate of vascular perfusion.3. The apparent size of the tissue pool(s) of 3MG that have to be loaded to achieve the steady state rate of transfer are less than those that unload into the vascular bed after 3MG is removed from the intestinal lumen. This ;up-down asymmetry' is abolished when phlorizin is present in the intestinal lumen during the unloading phase.4. When 3MG is abruptly removed from the intestinal lumen after the tissue has been previously loaded with the sugar, the rate of washout into the vascular bed can be described by the sum of two exponential terms. The two terms differ in that the rate constant of the earlier ;fast' term is sensitive to the rate of vascular perfusion, while the later, ;slow', rate constant is insensitive to flow rate. The total quantity of 3MG that can be unloaded from the tissue into the portal venous effluent is decreased when phlorizin is present in the intestinal lumen during the unloading phase.5. Absorption from the lumen of the anuran intestine continues while the mesenteric circulation is interrupted. An estimate of the concentration of 3MG during the period of vascular stoppage can be made from the quantity recovered in the portal venous effluent when vascular perfusion is reinstituted (;vascular stop-flow'). The extent of the accumulation depends upon the duration of the vascular stoppage and the presence of Na ions in the intestinal lumen is essential for accumulation to occur.6. The findings are discussed in relation to the transfer of 3MG between various possible compartments in the tissue during absorption. Evidence is presented that a re-uptake of previously absorbed 3MG may occur across the brush border membrane. Such a recycling of 3MG across the epithelium implies that the apparent unidirectional fluxes measured across the epithelium between the bulk phase of the lumen and the blood may underestimate the size of fluxes across the epithelium at the cellular level.

Animals↗

Factors affecting the utilization of ketone bodies and other substrates by rat jejunum: effects of fasting and of diabetes.

1. The utilization of some metabolic fuels has been measured in vitro in a preparation of rat jejunum to which the substrates were supplied via the perfusate flowing through the vascular bed. 2. In jejunum from 48 hr-fasted rats, the combined rates of utilization of 1 mM-acetoacetate and 2mM-D-3-hydroxybutyrate are similar to that of 7.5 mM-glucose. 3. The utilization of glucose is reduced in jejunum from animals fasted for 48 hr (45--63% reduction) and also from animals after 3--6 days of diabetes induced by streptozotocin (29% reduction). The addition of ketone bodies or of Na-oleate to the vascular perfusate does not reduce the utilization of glucose by the jejunum of either fed or 48 hr fasted rats. 4. Ketone bodies in the vascular perfusate reduce the oxidation of glucose by the jejunum of fed rats. In the jejunum of 48 hr-fasted rats, ketone bodies completely inhibit the oxidation of glucose so that all the glucose utilized by the tissue is converted to lactate. 5. The findings are discussed in relation to other work and it is concluded that substrates for the oxidative metabolism of the jejunum of fasted rats are likely to be ketone bodies, glutamine and fatty acids; at the same time the utilization of glucose is reduced and its oxidation completely abolished.

Animals↗

The utilization of glucose and production of lactate by in vitro preparations of rat small intestine: effects of vascular perfusion.

1. The rate of metabolism of glucose to lactate has been measured in a number of non-vascularly perfused preparations of rat jejunum in vitro. The glucose and lactate metabolism was measured simultaneously and under conditions such that the uptake of glucose and the appearance of lactate were linearly related to time. 2. It is found that there is no difference between the rates at which rings of rat jejunum utilize glucose during the first 45 min of anaerobic or aerobic incubation. During the first 15 min of incubation between 60-70% of the metabolized glucose was converted to lactate under aerobic conditions; this value increased to 80-90% during the subsequent 30 min. During the period 0-15 min of incubation, lactate production was found to be higher under anaerobic than under aerobic conditions but after this initial period the rate of lactate production was the same under aerobic and anaerobic conditions. 3. For segments of rat jejunum, maintained in vitro by the recirculation of nutrient fluid through the intestinal lumen, neither the rate of production of lactate, nor the utilization of glucose, was stimulated if the preparation was maintained under anaerobic rather than aerobic conditions. The direct delivery of gas into the intestinal lumen in the form of a stream of bubbles (segmented circulation) reduced both the utilization of glucose and the production of lactate under aerobic conditions. However, not effect on glucose metabolism was observed under anaerobic conditions. The finding of a Pasteur effect with the segmented-circulated preparation, but not with the simple recirculated preparation, is associated with lower rate of aerobic lactate production in the former preparation. Reasons are given for supposing that under conditions of segmented circulation, the luminal compartment is better stirred, thereby increasing access of O2 to the tissue. 4. A preparation of rat small intestine perfused through the vascular bed is described. With this preparation the rate of glucose utilization is significantly lower than that for recirculated preparations and the rate of lactate production is substantially less than that of the other preparations studied. 5. With the preparation perfused through the vascular bed, and with glucose, 10 mM, present only in the vascular medium the addition of erythrocytes to the vascular infusate causes a significant reduction in both glucose utilization and in the rate of lactate production. The addition of erythrocytes to produce an haematocrit of 40% (v/v) causes a greater reduction in glucose utilization and lactate production than is found for an haematrocrit of 15%. About 10% of the lactate produced appears in the luminal contents. With an haematocrit of 15%, the O2 consumption of the whole wall of the jejunum was found to be 6-4 mumole O2 g dry wt.-1 min-1, equivalent of a value for the Q02 of 8-6 mul. O2 mg druwy wt.-1 hr-1. The uptake of O2 was almost entirely from the vascular infusate. 6...

Aerobiosis↗