bluuebunny/crossref_metadata_2025 huggingface dataset:
Steroid secretion by in vitro perfused testes: testosterone biosynthetic pathways.
Authors: Chubb C , Ewing L L
Published: December 2017

Alternative metabolic pathways for the biosynthesis of testosterone from pregnenolone exist in mammalian testes. The following experiments were designed to identify the preferred testosterone biosynthetic pathway in rat and rabbit testes. The experimental protocol included the infusion of steroidogenic reaction inhibitors and testosterone biosynthetic intermediates into testes perfused in vitro. Under these conditions, the testicular steroid secretions were a measure of specific reaction activities. Infusion of medrogestone (6,17-dimethyl-4,6-pregnadiene-3,20-dione, Ayerst), an inhibitor of delta5-4isomerization, permitted the reactions converting pregnenolone to androstenediol to be studied separately from those converting progesterone to testosterone. For example, the activity of the pregnenolone vector 17alpha-hydroxypregnenolone reaction was measured as the total of the 17alpha-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol secreted by medrogestone-inhibited testes. The reactions convering delta5-3beta-hydroxysteroids to delta4-3-ketosteroids were studied in testes infused with SU-10603 (7-chloro-3,4-dihydro-2-[3-pyridyl]-1(2H)-naphthalenone. Ciba-Geigy), an inhibitor of 17alpha-hydroxylation and C-17, C-20 cleavage reactions. The results indicated that preferred testosterone biosynthetic pathways are present and different in rat and rabbit testes.
Lymph capillary pressure of rat intestinal villi during fluid absorption.
Authors: Lee J S
Published: December 2017

A newly developed intestinal preparation is described for determining lymph capillary pressure (PL) in the villi in vivo and in vitro. Determination of PL provided an estimate of tissue fluid pressure in the villi. PL was related to the fluid absorption rate and increased by lymphatic obstruction. During fluid absorption from isotonic mucosal fluid, PL was 1.4 +/- 0.5 or 1.1 +/- 0.4 cmH2O determined in vivo or in vitro, respectively. Both pressures were essentially in the same range as that (0.7 +/- 0.3--1.3 +/- 0.5 cmH2O) in which the mucosal fluid was isotonic Na2SO4 solution or Na-free solutions from which little fluid absorption occurred. This range of pressures may be taken as the normal tissue fluid pressure in the villi. At a high rate of fluid absorption from hypotonic mucosal fluid, PL increased to 5.2 +/- 1.4 cmH2O and tissue fluid pressure was also similarly increased. It is concluded that the fluid absorptive process by the epithelium could not develop an appreciable hydrostatic pressure in the villus tissue space or in the lymphatics.
Transport of protein-bound steroid hormones into liver in vivo.
Authors: Pardridge W M , Mietus L J
Published: December 2017

The unidirectional influx of 3H-gonadal (progesterone, dihydrotestosterone, testosterone, estradiol) and adrenal (aldosterone, cortisol) steroid hormones into liver was studied with a tissue-sampling single-injection technique in barbiturate-anesthetized rats. Liver uptake of the steroid hormone was measured relative to [14C]butanol, a highly diffusible reference, after a single pass through the liver. Portal flow (1.4 ml.min-1.g-1) under the experimental conditions was measured with 3H2O. The extraction of unidirectional influx of all six steroid hormones was 70-100% after a bolus portal injection of labeled steroid in Ringer solution (0.1% albumin). Steroid transport was nonsaturable because 35 muM concentrations of unlabeled hormone resulted in no inhibition of liver transport. The plasma proteins (albumin and specific globulins) in serum from human (male, female, pregnancy), rat (male), and guinea pig (pregnancy) sources inhibited the liver clearance of the respective steroid hormones to a variable extent. In all cases albumin-bound steroid hormone was freely cleared by liver and, in the case of cortisol or estradiol, the fraction bound to a specific globulin was also transported into liver.
Thermogenic effect of thyroid hormones: interactions with epinephrine and insulin.
Authors: Piolino V , Acheson K J , Müller M J , Jeanprêtre N , Burger A G , Jéquier E
Published: December 2017

The interactions between thyroid hormones, epinephrine, and insulin in the regulation of energy expenditure were investigated in a group of healthy young men before and after thyroxine (T4) treatment (300 micrograms/day for 14 days) at basal plasma insulin concentrations and during hypoinsulinemia with and without epinephrine infusion (0.05 micrograms.kg fat-free mass-1.min-1). T4 treatment induced moderate hyperthyroidism and increased resting energy expenditure (RMR). The effect was more pronounced during short-term hypoinsulinemia, but hypoinsulinemia by itself did not influence RMR. Epinephrine infusion caused a significant increase in energy expenditure. The effect was most pronounced at hypoinsulinemia and with T4 treatment. Hypoinsulinemia and T4 treatment were not additive in their effects. We conclude that basal insulin concentrations mask some of the thermogenic effects of thyroid hormones and epinephrine. Thus insulin antagonism may suppress some of the thermogenic actions of thyroid hormones and epinephrine.
Mechanism of atrial natriuretic factor-induced inhibition of rat mesangial cell mitogenesis.
Authors: Appel R G
Published: December 2017

Recent observations suggest that atrial natriuretic factor (ANF) may have growth-inhibitory activity. The present studies were performed to further define this action in rat mesangial cells (which have both biological and clearance ANF receptors) and in 3T3 fibroblasts (which have only clearance ANF receptors). Both cell types were made quiescent by removal of serum and then reactivated by exposure to a serum-free defined medium. ANF inhibited [3H]thymidine uptake in a dose-dependent manner in mesangial cells (half-maximal response 10(-11) M; 47% maximal inhibitory effect) but had no effect in 3T3 fibroblasts. Exogenous 8-bromoguanosine 3',5'-cyclic monophosphate (0.1 mM) inhibited [3H]thymidine uptake by 33% in mesangial cells but had no effect in 3T3 fibroblasts. Counts in mesangial cells exposed to 0.1 mM sodium nitroprusside, which stimulates guanosine 3',5'-cyclic monophosphate (cGMP), were inhibited by 76%. However, this represented a toxic effect, because excessive trypan blue uptake was noted in this condition. Mesangial cell number after 3 days of logarithmic proliferation was reduced by 33% in cells incubated with 1.0 nM ANF compared with vehicle. Incubation of mesangial cell monolayers with ANF caused a concentration-dependent increase in intracellular cGMP accumulation. Threshold responses occurred at concentrations one order of magnitude greater than that resulting in the antimitogenic action. In 3T3 fibroblast monolayers exposed to ANF, cGMP accumulation occurred but was markedly attenuated compared with mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Systemic pH modifies ketone body production rates and lipolysis in humans.
Authors: Hood V L , Keller U , Haymond M W , Küry D
Published: December 2017

To investigate whether changes in systemic pH influence ketone body production or utilization, total ketone body (TK) kinetics were measured with [3-14C]acetoacetate and D-beta-[1,3-13C2]hydroxybutyrate tracers in overnight fasted subjects during metabolic alkalosis (NaHCO3 infusion) or acidosis [NH4Cl ingestion or arginine (Arg)-HCl infusion]. Somatostatin, with insulin, glucagon, and growth hormone replacement, was infused in all studies. Blood pH and HCO3- (mM) increased from baseline (0-30 min) to 180-210 min by 0.08 +/- 0.02 and 7 +/- 1 with NaHCO3 and decreased by 0.08 +/- 0.2 and 7 +/- 1 or 5 +/- 1 with NH4Cl or Arg-HCl (all P less than 0.005). Over this period blood TK (microM) differed between the NaHCO3 (+198 +/- 65) and both NH4Cl (-90 +/- 53) and Arg-HCl (-154 +/- 55) (P less than 0.05). These changes resulted from parallel alterations in TK production rate of appearance (Ra TK, mumol.kg-1.min-1), because changes from baseline in Ra 14C TK also differed between NaHCO3 (+1.9 +/- 0.8) and NH4Cl (-1.0 +/- 0.6) and Arg-HCl (-2.0 +/- 0.5) (P less than 0.05). Ra TK calculated with single- or dual-tracer techniques were similar. Blood free fatty acids (FFA) increased with NaHCO3, and FFA and glycerol decreased with NH4Cl and Arg-HCl, suggesting that FFA availability mediated the pH effects on hepatic ketogenesis. These results demonstrate that modest changes in systemic pH modify FFA availability and TK production rates.
Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans.
Authors: Virkamäki A , Puhakainen I , Nurjhan N , Gerich J E , Yki-Järvinen H
Published: December 2017

To assess the validity of determining the origin of plasma lactate from the ratio of lactate and glucose specific activities (SA) during infusion of labeled glucose, normal subjects received infusions of [6-3H]- and [6-14C]glucose for 4 h after a 12 h fast, and, on another day, cold glucose labeled with both tracers during 4-6 h of hyperinsulinemia (approximately 650 microU/ml). Basally, less lactate was derived from plasma glucose when measured with [6-3H]glucose (27 +/- 2%) than with [6-14C]glucose (40 +/- 2%, P less than 0.001). Insulin did not increase the percent of lactate derived from plasma glucose when measured with [6-3H]glucose (29 +/- 2%) but did increase when measured with [6-14C]glucose (60 +/- 4%). The arterialized blood (A) [3H]lactate SA was 30-40% higher (P less than 0.01) than deep venous blood (V) [3H]lactate SA, whereas A and V [14C]lactate SA were similar. During conversion of alanine to lactate with glutamic-pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in vitro, 32 +/- 2% of 3H in [3-3H]alanine was found in water and 68 +/- 2% in lactate. During infusion of [6-3H]- and [6-14C]glucose, the ratio of [14C]alanine to lactate SA (0.88 +/- 0.05) was less than the ratio of [3H]alanine to lactate SA (0.31 +/- 0.03, P less than 0.001). In conclusion 1) loss of 3H relative to 14C from position 6 in glucose occurs during lactate formation in extrahepatic tissues possibly due to the GPT reaction (alanine conversion to pyruvate), and 2) even under supraphysiologic hyperinsulinemic conditions not all of plasma lactate originates from plasma glucose.
Age-related differences in norepinephrine kinetics: effect of posture and sodium-restricted diet.
Authors: Supiano M A , Linares O A , Smith M J , Halter J B
Published: December 2017

We used compartmental analysis to study the influence of age on the kinetics of norepinephrine (NE) distribution and metabolism. Plasma NE and [3H]NE levels were measured in 10 young (age 19-33 yr) and 13 elderly (age 62-73 yr) subjects in the basal supine position, during upright posture, and after 1 wk of a sodium-restricted diet. We found that the basal supine release rate of NE into the extravascular compartment, which is the site of endogenous NE release (NE2), was significantly increased in the elderly group (young, 9.6 +/- 0.5; elderly, 12.3 +/- 0.8 nmol.min-1.m-2; means +/- SE; P = 0.016), providing direct evidence for an age-related increase in sympathetic nervous system (SNS) tone. Although upright posture led to a greater increase in plasma NE in the young (0.90 +/- 0.07 to 2.36 +/- 0.16 nM) than in the elderly (1.31 +/- 0.11 to 2.56 +/- 0.31 nM; age group-posture interaction, P = 0.02), the increase in NE2 was similar between the young (9.6 +/- 0.6 to 16.2 +/- 1.5 nmol.min-1.m-2) and the elderly (11.6 +/- 1.4 to 16.1 +/- 2.4 nmol.min-1.m-2; posture effect, P = 0.001; age group-posture interaction, P = 0.15). Thus the increase in SNS tone resulting from upright posture was similar in young and elderly subjects. Plasma NE levels increased similarly in both groups after a sodium-restricted diet (diet effect, P = 0.001; age group-diet interaction, P = 0.23). However, NE2 did not increase significantly in either group (diet effect, P = 0.26), suggesting that SNS tone did not increase after a sodium-restricted diet. Compartmental analysis provides a description of age-related differences in NE kinetics, including an age-related increase in the extravascular NE release rate.
A stimulatory effect of FFA on glycolysis unmasked in cells with impaired oxidative capacity.
Authors: Blackard W G , Clore J N , Powers L P
Published: December 2017

The physiological importance of the glucose fatty acid cycle has been controversial. Many studies have failed to demonstrate an inhibitory effect of free fatty acids (FFA) on glucose utilization. Using both hepatoma cells (Hep G2) and human erythrocytes, which have poor oxidative capacity and metabolize glucose primarily anaerobically, we have demonstrated a unique stimulatory effect of FFA on glycolysis. Fructose 2,6-bisphosphate (F-2,6-P2) concentrations also increased significantly in Hep G2 cells incubated with palmitic acid. In contrast, F-2,6-P2 concentrations fell in primary cultured hepatocytes incubated with palmitic acid in association with increased oxidation of FFA and accumulation of beta-hydroxybutyrate. We propose that a stimulatory effect of FFA on glycolysis reported here for the first time may have been masked in previous studies performed in tissues in which the oxidation of FFA and the accumulation of intermediates such as citrate may have decreased F-2,6-P2 concentrations. We conclude that the spectrum of FFA effects in glycolysis probably depends on tissue oxidative capacity.
Lactate in rat skeletal muscle after hemorrhage measured by microdialysis probe calibrated in situ
Authors: Okuda C. , Sawa T. , Harada M. , Murakami T. , Matsuda T. , Tanaka Y.
Published: December 2017

The interstitial lactate concentration in rat skeletal muscle was measured in the normal state and after hemorrhage using a microdialysis probe, and the values calculated by in vitro and in vivo calibration were compared. After withdrawal of 30% of the estimated total blood volume, the lactate concentration in the dialysate gradually increased and then maintained an almost constant level. It was found that interstitial lactate levels of skeletal muscle calculated by the in vitro calibration method were not significantly different from those calculated by in vivo calibration in both the normal state and after hemorrhage. These data indicate that the absolute lactate concentration in the muscle interstitium in the normal state and after acute hemorrhage can be practically measured by a microdialysis probe calibrated in vitro. From the comparison of lactate concentrations in blood and in the muscle interstitium, it was suggested that rat skeletal muscle functions as a lactate consumer, rather than as a lactate producer, after acute hemorrhage.
Effect of moderate cold exposure on 24-h energy expenditure: similar response in postobese and nonobese women
Authors: Buemann B. , Astrup A. , Christensen N. J. , Madsen J.
Published: December 2017

Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were measured two times in eight postobese women and eight matched controls. On one occasion the subjects were exposed to a room temperature of 16 degrees C, on the other to 24 degrees C. Cold exposure elicited a 2% increment in 24-h EE (P < 0.05), with similar response in the two groups. The slight increase in EE was entirely covered by an enhanced carbohydrate oxidation rate. Fasting plasma norepinephrine (NE) increased from 0.74 +/- 0.08 to 1.29 +/- 0.21 nmol/l under cold exposure (P < 0.05), with no group difference. The cold-induced increase in 24-h EE was positively correlated to the increase in NE concentration (r2 = 0.41, P = 0.01). Sleeping EE was found to be 5% lower in the postobese women than in the controls (P = 0.04). The postobese group also had higher 24-h nonprotein respiratory quotient than the control group (P = 0.04), which was due to a 26% lower lipid-to-carbohydrate oxidation ratio. The study demonstrates that the thermogenic response to cold is normal in women susceptible to obesity, but it supports previous reports of a slightly lower basal EE and lower lipid-to-carbohydrate oxidation ratio in postobese subjects.
Chronic infusion of TNF-alpha reduces plasma T4 binding without affecting pituitary-thyroid activity in rats
Authors: Sweep C. G. , van der Meer M. J. , Ross H. A. , Vranckx R. , Visser T. J. , Hermus A. R.
Published: December 2017

In the present study the effects of continuous administration of tumor necrosis factor-alpha (TNF-alpha), in a dose not affecting body temperature and food intake, on pituitary-thyroid function of rats were investigated. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps that continuously delivered recombinant human TNF-alpha (8.0 micrograms/day ip) or saline for 7 days. Infusion of TNF-alpha resulted in a significant decrease of plasma total thyroxine (T4) levels during days 2-5 of infusion as compared with the levels in saline-infused rats. This suppression of plasma T4 concentrations was caused by a decreased binding of T4 in plasma, as indicated by an increased percentage of free T4. TNF-alpha infusion did not significantly affect free T4 levels in plasma nor basal and thyrotropin-releasing hormone-stimulated TSH levels. The decreased binding of T4 was, at least partially, caused by a reduction of T4-binding prealbumin (TBPA) levels in plasma, which were significantly reduced during the first 3 days of TNF-alpha infusion. Plasma levels of free fatty acids were not affected by TNF-alpha. TNF-alpha treatment did not influence the plasma 3,5,3'-triiodothyronine (T3)-to-T4 ratio nor hepatic 5'-deiodinase activity. Plasma reverse T3 levels remained undetectable both in control and TNF-alpha-treated rats. Taken together, our findings indicate that chronic infusion of rats with TNF-alpha in a subpyrogenic and subanorectic dose induces a transient decrease of plasma T4 binding without affecting pituitary-thyroid activity and peripheral thyroid hormone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic acidosis reverses the increase in serum 1,25(OH)2D in phosphorus-restricted normal men
Authors: Portale A. A. , Halloran B. P. , Harris S. T. , Bikle D. D. , Morris R. C.
Published: December 2017

We tested the hypothesis that in humans, metabolic acidosis can disorder the metabolism of 1,25-dihydroxyvitamin D [1,25(OH)2D] by impairing the capacity for a sustained physiological stimulus to increase renal production of this hormone. Specifically, in seven healthy men in whom restriction of dietary phosphorus had doubled their serum concentration of 1,25(OH)2D, we induced metabolic acidosis of moderate severity with oral NH4Cl, administered for 7 days. With induction of acidosis, the serum concentration of 1,25(OH)2D decreased sharply and remained decreased and near constant throughout the period of acidosis, the decrease amounting to one-half of the increment induced by phosphorus restriction alone. The serum concentration of free 1,25(OH)2D also decreased, since the measured free fraction of 1,25(OH)2D was unaffected by NH4Cl. The decrease in serum 1,25(OH)2D was accounted for by a 16% increase in its metabolic clearance rate and by a 19% decrease in its production rate. Metabolic acidosis induced a modest increase in the concentrations of blood ionized calcium and serum phosphorus. Multiple linear regression analysis revealed that serum levels of 1,25(OH)2D varied inversely and significantly with those of plasma hydrogen ion (R = -0.77, P < 0.001), but not with those of blood ionized calcium or serum phosphorus. These data demonstrate in humans that metabolic acidosis can substantially reverse the increase in serum concentration of 1,25(OH)2D induced by phosphorus restriction. The data provide evidence that acidosis can restrict the increase in renal production and serum concentration of 1,25(OH)2D effected by a sustained physiological stimulus.
Effects of gastrointestinal polypeptides on hormone content of endocrine pancreas in the rat
Authors: Yamada T. , Solomon T. E. , Petersen H. , Levin S. R. , Lewin K. , Walsh J. H. , Grossman M. I.
Published: December 2017

Although trophic actions of gastrointestinal peptides on exocrine pancreas have been shown, little is known regarding their effects in endocrine pancreas. Therefore, we measured the contents of somatostatin-like immunoreactivity (SLI), insulin and glucagon, in pancreatic extracts from rats that had been treated three times a day for 10 days with saline; 1 microgram/kg caerulein; 5, 25, and 100 microgram/kg secretin; 1 microgram/kg caerulein plus 5, 25, and 100 microgram/kg secretin; 25 microgram/kg pancreatic polypeptide; 15 microgram/kg glicentin; or 15 microgram/kg gastric-inhibitory polypeptide. Pancreatic SLI content was significantly increased in rats treated with glicentin and caerulein plus secretin at the two higher doses. No difference was noted between the control and the caerulein plus 100 microgram/kg secretin groups in delta-cell number per islet when examined by the immunoperoxidase technique. These data suggest that because of their effect on SLI content gastrointestinal polypeptides may modulate pancreatic endocrine function.
Metabolism in man of 7-ketolithocholic acid: precursor of cheno- and ursodeoxycholic acids
Authors: Fromm H. , Carlson G. L. , Hofmann A. F. , Farivar S. , Amin P.
Published: December 2017

To define the metabolism of 7-ketolithocholic acid in man, studies were carried out in gallstone patients with normal liver function. 7-[24-14C]ketolithocholic acid or its glycine or taurine conjugates were injected intravenously, and the chemical form of radioactivity appearing in bile was determined to define hepatic biotransformation. To study intestinal absorption 7-[24-14C]ketolithocholic acid was infused into the jejunum and ileum, respectively, and the chemical form of radioactivity appearing in peripheral blood and bile was assessed. 7-Ketolithocholic acid was extensively reduced in the liver to chenic acid and, to lesser extent, to ursodeoxycholic acid. Hepatic reduction was similar for both unconjugated as well as glycine- and taurine-conjugated 7-ketolithocholic acid. 7-Ketolithocholic acid was well absorbed. There was no biotransformation in the small intestinal lumen or during absorption, because all radioactivity recovered from the lumen or in peripheral blood was in unchanged 7-ketolithocholic acid. Biotransformation products in bile after jejunal infusion were similar to those after intravenous injection. The studies indicate that 7-ketolithocholic acid is likely to be a physiological precursor of ursodeoxycholic acid in healthy man.
Properties of the cat ileocecal sphincter muscle
Authors: Cardwell B. A. , Rubin M. R. , Snape W. J. , Cohen S.
Published: December 2017

The purpose of this study was to determine the length-tension properties and the response to neurohumoral agents of the feline ileocecal sphincter (ICS) circular smooth muscle in vitro. The ICS muscle during stretch maintained a higher resting tension at lower degrees of stretch than did the adjacent ileum and colon. Sodium nitroprusside (10(-3) M) or calcium-free Krebs solution with EGTA (5.0 mM) reduced the resting tension of ICS muscle by 15.8 +/- 2.1 and 19.1 +/- 2.5%, respectively. The ICS response to KCl depolarization was lower (0.37 +/- 0.03 kg/cm2) than colonic muscle (0.55 +/- 0.06 kg/cm2) oe ileal muscle (0.51 +/- 0.04 kg/cm2) (P less than 0.05). However, in response to acetylcholine, ICS muscle tension was minimal (0.06 +/- 0.02 kg/cm2) was compared with the colon (0.49 +/- 0.05 kg/cm2) or ileum (0.53 +/- 0.05 kg/cm2) (P less than 0.01). The ICS muscle contracted in response to phenylephrine, whereas other muscles were inhibited. Secretin, gastrin, glucagon, and cholecystokinin failed to act on the ICS muscle while other muscles did respond. These studies suggest that ICS muscle differs from adjacent ileal and colonic circular muscle in that a) in response to stretch it develops a high resting tension that is relatively resistant to calcium withdrawal, and b) it also shows quantitative and qualitative differences in response to neurohumoral agents.
Gastric alkaline response to mucosa-damaging agents: effect of 16,16-dimethyl prostaglandin E2
Authors: Swierczek J. S. , Konturek S. J.
Published: December 2017

We investigated the effects of luminal application of graded concentrations of conventional mucosal barrier breakers such as ethanol, aspirin (ASA), and sodium taurocholate (TCh), as well as 16,16-dimethyl prostaglandin E2 (DMPGE2) on gastric alkaline output (GAO) and transmucosal potential difference (PD). The Lucite chamber stomach-flap preparation was used in 50 dogs whose basal H+ secretion was inhibited by intravenous cimetidine. Graded concentrations of ethanol, and TCh at pH 5.0, and acidified solutions of ASA (at pH 5.0--2.0) were found to produce a dose-dependent increase in GAO accompanied by a stepwise decline in PD. Increasing concentrations of DMPGE2 above 1.0 microgram/ml caused a dose-related increase in GAO and a reduction in PD. The combination of DMPGE2 with ethanol aggravated the PD changes, whereas GAO induced by these agents was decreased. Alterations in GAO and PD evoked by the ASA solutions varying in pH were not significantly affected by the addition of 1.0 microgram/ml DMPGE2 to the bathing fluid. These results indicate that stimulation of gastric alkalinization with concomitant fall in PD is a common feature for various mucosa-irritant substances, and pretreatment with DMPGE2 does not prevent these effects.
Demonstration of net potassium absorption in mammalian colon
Authors: Hayslett J. P. , Halevy J. , Pace P. E. , Binder H. J.
Published: December 2017

The present in vivo studies were performed in the rat to determine whether the colon was capable of net potassium absorption, as well as secretion, and to further elucidate the process responsible for net potassium movement. Both the proximal and distal lumina of the colon of control, potassium-deficient, and potassium-loaded animals were perfused with solutions containing either 140 or 20 mmol/l sodium. Net potassium secretion was present in both proximal and distal colon of control animals during perfusion with the 140 mmol/l sodium solution. The rate of net potassium secretion was reduced in the potassium-deficient animals. During perfusion with the 20 mmol/l sodium solution, the rate of potassium secretion was also reduced (compared with control perfusion solution) in both the control and potassium-deficient animals. As a result, there was net potassium absorption (0.94 +/- 0.14 mueq.1-1.g dry wt-1) and zero net potassium movement in the distal and proximal segments, respectively, of the potassium-deficient animals perfused with the low-sodium solution. Additional studies were performed to determine whether net potassium secretion was saturable and showed that, during progressive increases in the plasma potassium level, net secretion was constant at plasma potassium levels above 11-13 meq/l. These data, therefore, demonstrate that the mammalian colon regulates intestinal transport of potassium by both absorptive and secretory mechanisms and that a carrier-mediated process probably regulates both transport processes.
Cytoprotective effect of centrally administered neurotensin on stress-induced gastric ulcers
Authors: Nemeroff C. B. , Hernandez D. E. , Orlando R. C. , Prange A. J.
Published: December 2017

Neurotensin, a peptide common to brain and gastrointestinal tissue, has been reported common to brain and gastrointestinal tissue, has been reported to inhibit both gastric acid secretion and gastric mucosal blood flow after central nervous system administration in rats. Therefore, the effect of intracisternal neurotensin on the development of gastric ulcers induced by cold-plus-restraint stress in the rat was studied. Following intracisternal injection, neurotensin (20-30 micrograms) significantly inhibited the development of gastric ulcers in this model. This effect was shown to be both dose related and route specific, inasmuch as neither lower doses of intracisternal neurotensin nor intravenous neurotensin were cytoprotective. In addition, potential actions of central neurotensin that may have mediated this beneficial effect were tested by administering somatostatin or oxotremorine intracisternally and cimetidine or haloperidol intraperitoneally. In contrast to intracisternal neurotensin, none of these substances reduced the incidence of gastric ulcers in this model. This was true despite the fact that cimetidine, but not neurotensin, significantly increased gastric pH. Finally, when cold-plus-restraint-stressed rats were pretreated with indomethacin, an inhibitor of prostaglandin synthesis, the cytoprotective effect of neurotensin was completely abolished. These results suggest that intracisternal neurotensin exerts a significant cytoprotective effect for stress-induced gastric ulcers in rats. This effect, which is mediated by the central nervous system, does not appear to be related to changes in body temperature, neuroleptic-like properties, or gastric acid secretion but requires an intact prostaglandin synthetic pathway.
Decreased pancreatic exocrine response to cholecystokinin in Zucker obese rats
Authors: McLaughlin C. L. , Peikin S. R. , Baile C. A.
Published: December 2017

Cholecystokinin (CCK), one of the peptides secreted by the gastrointestinal tract during a meal, stimulates release of enzymes into pancreatic juice and is a trophic hormone for the pancreas. Administration of CCK also decreases food intake, and obese rats have been shown to have a higher threshold than lean rats for this apparent effect on satiety. In this study experiments were designed to compare the sensitivity of obese and lean rats to the effects of CCK octapeptide (CCK-8) on pancreatic structure and exocrine function. In both growing and adult Zucker rats DNA content of the pancreas from obese rats was decreased compared with that from lean rats [2.42 +/- 0.21 vs. 3.07 +/- 0.18 mg (P less than 0.01) and 2.46 +/- 0.25 vs. 3.01 +/- 0.19 mg (P less than 0.05), respectively], and in adult obese rats this was accompanied by decreased pancreas size on both absolute weight and percent of body weight bases. In adult obese Bar Harbor mice, although DNA content of the pancreas was also decreased [1.70 +/- 0.10 vs. 2.41 +/- 0.11 mg (P less than 0.01)], pancreas weight was not different (0.30 +/- 0.01 vs. 0.32 +/- 0.01 g). In young rats growth of the pancreas was stimulated by 2 micrograms/kg CCK-8 administered subcutaneously or 100 mg/kg of a trypsin inhibitor administered orally twice daily for 2 wk. Although both treatments increased weight and DNA and protein content of the pancreas, the increases in DNA and protein content were smaller in obese than lean rats, indicating a decreased responsiveness to both trophic agents. Administration of CCK-8 stimulated smaller increases in pancreatic juice volume and amylase release in obese compared with lean rats, indicating decreased pancreatic exocrine function in response to CCK. In adults the CCK-8 dose-response curve for amylase release from dispersed pancreatic acini of obese rats was similar to that of lean rats, indicating normal sensitivity in vitro. Thus, in obese rats and mice DNA content of the pancreas is decreased when compared with that of lean rats and mice, and this is accompanied by decreased in vivo responses to CCK in obese rats.
Effect of cycloheximide on corticosteroid-induced changes in colonic function
Authors: Charney A. N. , Wallach J. D. , Donowitz M. , Johnstone N.
Published: December 2017

Chronic parenteral mineralocorticoid and glucocorticoid treatment increases colonic sodium and water absorption and mucosal Na-K-ATPase activity. Cycloheximide, a protein synthesis inhibitor, was utilized to compare the mechanisms of action of these corticosteroids. Rats were injected with 50 or 100 micrograms/100 g body wet cycloheximide every 12 h, 0.5 or 3 mg/100 g deoxycorticosterone (DOCA) daily, or 3 mg/100 g methylprednisolone (MP) daily, singly or in combination for 2 days. In water absorption, transmural potential difference, and the specific activity of Na-K-ATPase were measured. Cycloheximide alone did not alter colonic water, sodium, or chloride absorption or Na-K-ATPase activity but did increase transmural potential difference. DOCA-induced increases in colonic absorption and Na-K-ATPase were completely prevented by cycloheximide. Cycloheximide completely prevented the increase in Na-K-ATPase in MP-treated rats but only partially reduced the MP-induced increase in sodium and water absorption. These results suggest that this enzyme is not the primary site of glucocorticoid action. It remains to be determined whether an increase in Na-K-ATPase activity is a necessary part of the maximal colonic response to chronic glucocorticoid treatment.
A defect of biliary excretion of copper in copper-laden Bedlington terriers
Authors: Su Le-Chu , Owen Charles A. , Zollman Paul E. , Hardy Robert M.
Published: December 2017

Copper-laden Bedlington terriers were found to absorb copper normally, based on the ratio of 64Cu in bile and in plasma ceruloplasmin after oral and intravenous doses of the radionuclide. The excessive accumulation of the copper in Bedlington terriers was due to impaired biliary excretion of the metal, The abnormal Bedlington pattern was simulated in normal dogs by biliary obstruction. Although the Bedlington terriers excreted more copper in their urine than normal, the amount was far less than that accumulated secondary to inadequate biliary excretion. These abnormalities are shared by patients with Wilson's disease, both conditions being inherited on an autosomal recessive basis.

copper absorption; copper excretion; radiocopper; Wilson's disease

Submitted on May 5, 1981

Accepted on March 30, 1982
Comparison of colonic and ileal propulsive capabilities under conditions requiring hydrostatic work
Authors: Weems W. A. , Weisbrodt N. W.
Published: December 2017

The intrinsic ability of cat colonic segments to do hydrostatic work to expel fluid was investigated in vitro and compared with the propulsive ability of ileal segments evaluated under identical conditions. Colonic segments spontaneously produced propulsive complexes at an average interval of 4.8 min when basal intraluminal pressure was set at 5 cmH2O. These complexes produced a net ejection of fluid in the aboral direction. When the capacitance of the evaluation system was set at 0.025 ml/cmH2O, colonic segments ejected only 5% of their content. This percentage increased to 23% when evaluation capacitance was increased to 0.125 ml/cmH2O. Peak aboral pressure associated with these complexes was approximately 37 cmH2O at both capacitances. Ileal segments aborally ejected almost twice as much fluid (44% of their luminal content) as did colonic segments at a capacitance of 0.025 ml/cmH2O even though ileal luminal content was five times less than colonic content. The aborally ejected volume per complex did not change when ileal segments were evaluated at two different capacitances even though higher pressures were required to eject fluid at the lower capacitance than at the higher capacitance. These results indicate that the propulsive behavior of ileal and colonic segments has some qualitative aspects that are similar but that only the propulsive ability of colonic segments is pressure limited under the conditions tested. Possible mechanisms that might produce this limitation are considered.
Electrical coupling of longitudinal and circular intestinal muscle
Authors: Elden L. , Bortoff A.
Published: December 2017

Space constants (lambda) were determined for longitudinal-circular muscle strips of cat jejunum by the partition method. Pulses of hyperpolarizing current spread along the major axes of circular muscle cells. In the absence of electrical coupling lambda measured from the longitudinal side of the strips should have been approximately 20 times shorter than lambda measured from the circular side. Median values were found to be statistically the same, 2.4 mm for the longitudinal side (n = 13) and 2.9 mm for the circular (n = 25). Methyl blue, iontophoretically injected into cells on the longitudinal side after recording large hyperpolarizing responses, was found in muscle cells located superficially in the longitudinal layer. The radial lambda for longitudinal muscle, determined from the change in magnitude of the hyperpolarizing response as the microelectrode was advanced through the layer, was 0.27 mm. This is too large to cause differences in depth of recording to significantly affect the circumferential lambda in this layer. These data provide evidence for a high degree of electrical coupling between the two muscle layers of cat jejunum.
Selective vasodilators redistribute intestinal blood flow and depress oxygen uptake
Authors: Shepherd A. P. , Riedel G. L. , Maxwell L. C. , Kiel J. W.
Published: December 2017

In this paper we report the effects of adenosine and isoproterenol on intestinal oxygen consumption. Using the recently developed technique of laser-Doppler velocimetry (LDV), we also studied the effects of these two agents on regional blood flow in the canine intestinal mucosa and muscularis. In isolated gut loops perfused at constant blood flow, both vasodilators depressed O2 uptake, but isoproterenol increased rubidium extraction while adenosine depressed rubidium extraction. Under constant pressure perfusion both dilators depressed O2 uptake but increased total flow. Isoproterenol increased the capillary filtration coefficient (Kf), but adenosine depressed Kf. LDV flowmetry showed adenosine increased muscularis flow and depressed mucosal flow. Both LDV flowmetry and radioactive microspheres showed isoproterenol increased mucosal but depressed muscularis flow. Our data indicate that the deleterious effects of isoproterenol and adenosine in depressing intestinal oxygen uptake can be explained by the ability of these agents to selectively vasodilate one of the regional circulations within the gut wall and by a "vascular steal" mechanism to reduce blood flow in the other vascular bed not as sensitive to the agent in question. The reduction in the regional blood flow thus depresses the O2 consumption of the gut as a whole. By comparing our regional laser-Doppler blood flow data with a simple analog model, we show that the seemingly paradoxical effect of vasodilators in depressing a regional blood flow while increasing total perfusion is explicable by a "vascular steal" mechanism.
Inhibition of short-circuit current in rat ileum by aliphatic alcohols
Authors: Fernandez Y. , Desjeux J. F. , Dumontier A. M. , Mitjavila S.
Published: December 2017

The importance of the hydrophobic nature of the membrane in certain functions of the intestinal epithelium was investigated by determining the variations in short-circuit current (Isc), potential difference (PD), and conductance (G) in rat ileum in the presence of the first eight alcohols in the n-aliphatic series. At the lowest alcohol concentrations and in the presence of Ringer-galactose, there was transitory stimulation of Isc and PD that did not occur in the presence of theophylline or in the absence of chloride. With or without theophylline all the alcohols tested inhibited Isc and PD and slightly increased G as a function of their concentration. The modifications in Isc were attributed to the inhibition of active sodium transport. These results demonstrate a linear relation between the logarithm of the concentrations causing 50% inhibition of Isc and the chain length of the alcohols. The variations in free energy required to transfer one -CH2- to the site at which the alcohols exert their activity were, respectively, -582 and -589 cal in the presence and absence of theophylline. These values show that the observed modifications in free energy are due to solubilization of the alcohols in a very hydrophobic zone of the tissue, confirming that the functional activities measured are dependent on the hydrophobicity of the membrane.
Reduced vascular sensitivity to norepinephrine in portal-hypertensive rats
Authors: Kiel J. W. , Pitts V. , Benoit J. N. , Granger D. N. , Shepherd A. P.
Published: December 2017

The development of portal hypertension following chronic portal vein stenosis is accompanied by a significant increase in intestinal blood flow. The present study was designed to determine whether intestinal vascular sensitivity to norepinephrine (NE) is also affected by chronic portal vein stenosis. Using a blood-perfused, in situ rat small intestine preparation, we found that, when compared with control animals, a significantly greater molar concentration of NE was required to achieve the same proportional increase in intestinal vascular resistance in portal-hypertensive animals. The mean ED50 value (+/-SE) for the portal-hypertensive group (704.3 +/- 186.1 nM) was significantly greater (P less than 0.05) than the mean ED50 value for the control group (271.4 + 48.1 nM). This finding implies that sympathetic maintenance of intestinal vascular tone may be impaired following chronic portal vein stenosis, possibly accounting for part of the intestinal hyperemia associated with portal hypertension.
Lymph flow, lymph protein concentration, and protein output from rat small intestine
Authors: Lee J. S.
Published: December 2017

Lymph flow (JL), lymph protein concentration (CL), and protein output (JP) from the main intestinal lymph duct were determined. The basal JL from the mesenteric pedicle alone was the same as that from the mesenteric pedicle attached with a segment of the nonabsorbing intestine, indicating that the basal JL does not originate from the intestine but is totally from the region of the mesenteric pedicle. The basal CL was 3.5-3.8 g/100 ml. When the intestine was absorbing water, JL increased and CL decreased, but JP increased above the basal JP in the initial 20 min of water absorption and then decreased progressively with time. Furthermore, it was estimated that CL in the "excess lymph" (formed during water absorption) was 1.4 +/- 0.2 g/100 ml in the initial 10 min of water absorption and was zero or nearly so in the later periods. From this and other evidence, it is concluded that under various conditions without net water absorption rat small intestine does not produce lymph and that during water absorption there is no significant increase in capillary permeability or capillary filtration. Therefore, the excess lymph could be mostly derived from the fluid absorbed from the lumen of the intestine.
Control mechanism of spontaneous in vitro contractions of the opossum sphincter of Oddi
Authors: Helm J. F. , Dodds W. J. , Christensen J. , Sarna S. K.
Published: December 2017

We evaluated the control mechanism of peristaltic contractions in the opossum sphincter of Oddi (SO) by means of an in vitro preparation. At each of four sites spaced uniformly along the sphincter segment, a force transducer recorded contractions while a monopolar electrode recorded myoelectric activity. Spontaneous myoelectric and contractile activity occurred in 15 of the 20 intact SO specimens studied. Electrical recordings showed characteristic control waves and response activity. Each control wave was invariably accompanied by a phasic contraction, irrespective of whether or not response activity was superimposed on the control wave. The predominant motor activity of the SO was antegrade peristalsis. Retrograde peristalsis occurred when antegrade peristalsis failed to traverse the entire sphincter. Spontaneous SO phasic contractions were not antagonized by tetrodotoxin. Muscle rings sectioned from the SO exhibited spontaneous phasic contractions with a proximal-to-distal gradient of intrinsic contraction frequencies. We conclude that a) the frequency of SO phasic contractions is determined by control wave frequency, b) spontaneous SO peristalsis is myogenic in origin and may be modeled by a linear array of bidirectionally coupled relaxation oscillators, c) the predominance of antegrade peristalsis may be explained by a high-frequency oscillator in the proximal SO that drives the slower, more distal oscillators, d) retrograde peristalsis is initiated by an ectopic oscillator in the distal SO when antegrade contractions fail to propagate the entire length of the SO, and e) ectopic SO contractions can propagate retrograde when the more proximal oscillators are not in their absolutely refractory state.
Thromboxane synthesis inhibition and postprandial intestinal hyperemia and oxygenation
Authors: Mangino M. J. , Chou C. C.
Published: December 2017

The effects of imidazole and U-63557A (Upjohn), inhibitors of thromboxane synthesis, on food-induced changes in intestinal blood flow and oxygen uptake were determined in the jejunum of anesthetized dogs. Intra-arterial (5.0 mg/min ia) infusions of imidazole had no effect on the postprandial intestinal hyperemia but significantly potentiated food-induced increases in oxygen uptake via enhanced oxygen extraction. Furthermore, imidazole had no effect on intestinal glucose absorption. The selective thromboxane synthesis inhibitor U-63557A (5 mg/kg iv) also enhanced oxygen uptake during nutrient absorption and had no effect on the hyperemia or glucose absorption. Our study indicates that inhibition of thromboxane synthesis has no effect on either resting intestinal blood flow or postprandial intestinal hyperemia but significantly enhances postprandial oxygen extraction and uptake. The potentiation of the food-induced increases in oxygen uptake by imidazole and U-63557A appears not to be related to glucose absorption. Endogenous thromboxane therefore appears to inhibit oxygen uptake more than blood flow, and yet does not affect glucose absorption during nutrient absorption.
Myoelectric correlates of colonic motor complexes and contractile activity
Authors: Sarna S. K.
Published: December 2017

This report describes the myoelectric correlates of colonic motor complexes and contractile activity. A set of four bipolar electrode/strain-gauge pairs was surgically implanted on the colon of each of the five dogs used in this study. Each recording site showed a cyclic occurrence of bursts of contractions called contractile states. The colonic muscle contracted mainly at two frequencies during a contractile state, long-duration contractions at 0.5-2 cycles/min and short-duration contractions at 4-6 cycles/min. The long-duration contractions at 0.5-2 cycles/min were associated with bursts of contractile electrical complex (electrical oscillations at 25-40 cycles/min) and continuous electrical response activity on a 1:1:1 basis. The short-duration contractions at 4-6 cycles/min were associated with bursts of discrete electrical response activity on a 1:1 basis. Those episodes of contractile electrical complex, continuous electrical response activity, and discrete electrical response activity that migrated orad or aborad over at least half the length of the colon were called colonic migrating myoelectric complexes. All other patterns of occurrence of these episodes were called colonic non-migrating myoelectric complexes. A total of 184 colonic migrating myoelectric complexes were recorded during a total recording period of 148 h: 173 migrated caudad and 11 orad. The mean period of colonic migrating myoelectric complexes was 52.7 +/- 6.5 (SE) min. We conclude that the characteristics of colonic migrating myoelectric complexes are strikingly different from those of migrating myoelectric complexes in the small intestine.