bluuebunny/crossref_metadata_2025 huggingface dataset:
Saturable binding of circulating peptide YY in the dorsal vagal complex of rats
Authors: Hernandez E. J. , Whitcomb D. C. , Vigna S. R. , Taylor I. L.
Published: December 2017

The rationale for this study was to test the hypothesis that peripherally released peptide YY (PYY) acts in the vagal nuclear complex of the medulla oblongata to modulate vagal tone centrally. The objective was to determine whether circulating PYY gains access to and binds to the receptors identified in the dorsal vagal complex (DVC) under physiological conditions. Specific brain regions were microdissected after intravenous 125I-labeled PYY and 131I-labeled bovine serum albumin infusions to determine saturable accumulation of PYY in the brain and to determine if there were changes in plasma volume with large PYY infusions. Significant (P < 0.05) saturable binding was observed in the region of the brain stem containing the DVC and the pituitary. There were no significant changes in plasma volume in any region after the infusion of the excess nonradioactive PYY. We conclude that under physiological conditions circulating PYY binds to sites in the pituitary and portions of the DVC that have PYY receptors and an incomplete blood-brain barrier but does not bind to other areas that have an intact blood-brain barrier. Therefore this peripheral hormone may act centrally to modulate the digestive system and is a member of a novel class of gut hormones that function as central neuromodulators.
Nucleotide receptors activate cation, potassium, and chloride currents in a liver cell line
Authors: Fitz J. G. , Sostman A. H.
Published: December 2017

By use of whole cell patch-clamp techniques, the effects of extracellular ATP on membrane ion currents of HTC cells from a rat liver tumor line were evaluated. ATP (500 microM) or the nonhydrolyzable analogue adenosine 5'-O-(3-thiotriphosphate) caused sequential activation of three currents: Icat (-1,325 +/- 255 pA at -80 mV) occurred early, was due to increased Na+ and K+ permeability, was present in 56% of 64 consecutive cells, and rapidly inactivated; IK (274 +/- 45 pA at 0 mV) was present in 59% of cells and also inactivated; and ICl (1,172 +/- 237 pA at +60 mV) was present in 94% of studies, was sustained, and exhibited outward rectification of the current-voltage relation. All three currents were present in 39% of cells. Increasing intracellular Ca2+ concentration ([Ca2+]i) by exposure to the 5'-nucleotide receptor agonist UTP (500 microM) or to thapsigargin activated Icat and IK but not ICl, whereas increasing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid in the pipette (> or = 5 mM) inhibited ATP-dependent activation of Icat and IK but not ICl. A P2x-preferring agonist alpha, beta-methylene ATP (500 microM) did not activate currents; a P2y-preferring agonist 2-methylthioadenosine triphosphate activated Icat and IK at concentrations of 500 microM but not 50 microM. In perforated patch recordings, ATP produced triphasic changes in membrane potential with initial depolarization due to Icat, subsequent hyperpolarization due to IK, and a later sustained depolarization due to ICl. These findings indicate that ATP modulates HTC cell ion permeability through initial activation of Icat and IK mediated by 5'-nucleotide receptors which mobilize [Ca2+], and sustained activation of ICl through a separate Ca(2+)-independent mechanism.
Clearance of surfactant-like particle proteins from circulation in rats
Authors: Yamagishi F. , Becich M. J. , Evans B. A. , Komoda T. , Alpers D. H.
Published: December 2017

Surfactant-like particles (SLP) have been isolated from the apical surface of rat enterocytes but appear to arise within the enterocyte and to be secreted into neighboring lymphatics (K. DeSchryver-Kecskemeti, R. Eliakim, S. Carroll, W. F. Stenson, M. A. Moxley, and D. H. Alpers. J. Clin. Invest. 84: 1355-1361, 1989). The present study was undertaken to analyze the clearance and distribution of these particle-associated proteins in vivo in the rat. Labeling of particles isolated from apical scrapings of rat enterocytes with 125I enabled identification of proteins of 116, 92, 68, 58, 48, 31, and 25 kDa. After the intravenous administration of 125I-SLP, the trichloroacetic acid-precipitable radioactivity in the plasma disappeared in a biphasic pattern. The average half-life of the early phase was 7.5 min and the second phase was 75 min. The half-life of a subset of the proteins (116, 92, and 48 kDa) was shorter, measuring 4.5 min for the first phase and ranging from 20 to 52 min for the second phase. The amounts of labeled particle distributed to the liver, kidney, and spleen were much greater than could be accounted for by distribution in the extracellular space alone. The liver accounted for removal of approximately 50% of label in the first phase, with the kidney and spleen contributing 10 and 1%, respectively. Only 0.5 and 2.5% of labeled protein appeared in the bile and urine, respectively. The majority of labeled protein remaining in the serum after the initial phase of tissue uptake migrated at a density of 1.07-1.08, characteristic of intact particles, but slowly shifted to higher densities over 24 h. The maximum binding capacity was 56 nmol/mg membrane protein (Michaelis constant = 51 pM) using hepatic basolateral membranes. The particle was taken up into hepatocytes, as demonstrated by autoradiography. These data demonstrate the importance of the liver in clearing SLP from the blood in rats. The slow clearance of a portion of the particle protein provides support for the continued presence of these proteins in the serum of rats.
Hepatic uptake of protein-bound ligands: extended sinusoidal perfusion model
Authors: Weisiger R. A. , Pond S. , Bass L.
Published: December 2017

Pages G872G884: R. A. Weisiger, S. Pond, and L. Bass. “Hepatic uptake of protein-bound ligands: extended sinusoidal perfusion model.” Page G879 (2nd column, 1st line): the sentence that reads “As for the standard model, the only fitted parameter was Pm, (resulting value 0.248 ± 0.051 cm/s)” should read “As for the standard model, the only fitted parameter was Pm, (resulting value 0.082 ± 0.004 cm/s).” The only effect of this error on the results and conclusions of this study is that the best-fit line in Fig. 3 is very slightly different in shape, with a correlation coefficient (r2) that still exceeds 0.999. The corrected figure is provided below.
Inhibition of nitric oxide formation in vivo enhances superoxide release by the perfused liver
Authors: Bautista A. P. , Spitzer J. J.
Published: December 2017

Nitric oxide, a known scavenger of toxic oxygen-derived radicals, has been shown to have a protective effect against tissue injury in endotoxemia. Based on the hypothesis that under normal physiological conditions, a balance between superoxide and nitric oxide exists in vivo, this work examines hepatic superoxide release after nitric oxide formation is inhibited in vivo. Male Sprague-Dawley rats were treated intravenously with N omega-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg body wt), an inhibitor of nitric oxide synthase. One hour later, superoxide anion release by the perfused liver was determined. Results show that a significant amount of superoxide was released after L-NAME treatment. Likely sources of this radical are the Kupffer cells. Inhibition of nitric oxide formation in vivo did not enhance superoxide release by hepatocytes or sinusoidal endothelial cells. The effect of L-NAME treatment on superoxide release in endotoxemic rats was also examined 12 h after lipopolysaccharide treatment, when toxic oxygen-derived radical formation could not be detected. Inhibition of nitric oxide release in vivo in these rats enhanced the formation of superoxide anion. The interaction between nitric oxide and superoxide anion under normal conditions may represent an important protective mechanism of the host against free radical damage.
Stimulation of duodenal motility by hyperosmolar mannitol depends on local osmoreceptor control
Authors: Lin H. C. , Elashoff J. D. , Kwok G. M. , Gu Y. G. , Meyer J. H.
Published: December 2017

Duodenal motility is stimulated by hyperosmolar solution. Since intestinal distension also stimulates intestinal motility, this increase in the motility response may be due to either stimulation of duodenal local osmoreceptor control or intestinal distension resulting from osmotic equilibration. To test which mechanism is primarily responsible for this osmotically sensitive effect, we compared the number of duodenal spike bursts in five dogs equipped with duodenal fistulas that allowed for the preservation or removal of intestinal distension. The response to 300 vs. 1,200 mosM mannitol was compared under three experimental perfusion methods: 1) distension was preserved both proximal and distal to the fistula (DD); 2) distension proximal to the fistula was removed (rD); and 3) distension both proximal and distal to the fistula was removed (rr). The test solutions had access to either the whole gut (DD and rD) or only the first 10 cm of the duodenum (rr). We found that 1) there were more spike bursts after the hyperosmolar solution (dose effect, P < 0.05, analysis of variance); 2) there was no significant difference between the three experimental methods; and 3) the stimulating effect of hyperosmolar solution depended on the first 10 cm of the duodenum. Thus, since hyperosmolar solution increased duodenal motility regardless of whether intestinal distension was preserved or removed, the stimulating effect of hyperosmolar solution on duodenal motility was primarily the result of a local osmoreceptor control mechanism located in the first 10 cm of the duodenum.
Renal excretion of N'1-methylnicotinamide in the rat
Authors: Ross CR , Diezi-Chomety F , Roch-Ramel F
Published: December 2017

The renal excretion of N'1-methylnicotinamide (NMN) was studied in the rat. Renal clearance experiments clearly demonstrated that: 1) NMN is secreted; 2)a tubularmaximum (Tm), 7 mumol/min per kg, could be reached; and 3)NMN secretion is inhibitedby a competitive inhibitor, mepiperphenidol. In free-flow micropuncture experiments, animals were infused with plasma concentrations of NMN ABOVE Tm; the TF/P NMNto TF/P inblin ratio for proximal and distal samples was 2.34 and 2.28, respectively, indicating that NMN is secreted in the proximal tubules and is not secreted orreabsorbed in the distal tubules. This finding was further confirmed by intratubularmicroinjections of ['14C]NMN into rats. In diuretic animals approxiamately 10%of the NMN injected into early proximal tubules was reabsorbed, but no reabsorption could be detected after distal injections. The nondiuretic animals showed no significant reabsorption of NMN. It was concluded that NMN transport is a carrier-mediated process and that reabsorption, if it occurs, plays only a minor role.
Effect of amygaloid lesions on gonadal maturation in male and female ferrets
Authors: Baum MJ , Goldfoot DA
Published: December 2017

Two experiments were performed to determine whether the amygdala is involved in theregulation of gonadal maturation in the ferret. In an experiment with prepuberal males it was found that testicular and epididymal wieghts, seminiferous tubule diameters, Leydid cell number, and ratings of spermatogenic development were the samein animals autopsied 4 wk after either the placement of a platinum-elctrode lesion in the amygdala or a sham operation. Testosterone concentrations both in testis and in blood tended to be lower, and body growth was significantly retarded in males with amygdaloid lesions. In a second experiment with prepuberal females it was found that the first estrus occurred significantly earlier in ferrets that had received amygdaloidlesions than in sham-operated controls. Neither body growth nor fertility of femaleswas affected. These findings suggest that the amygdala exerts an inhibitory influence on the hypothalamic mechanism which controls the secretion of gonadotropins required for initial estrus in female ferrets, but not for the initail masturation of the testes in males.
Factors influencing neurohumoral control of the heart in the newborn dog
Authors: Geis WP , Tatooles CJ , Priola DV , Friedman WF
Published: December 2017

Several investigators have documented immaturity of cardiac autonomic innervation in neonates. To evaluate the integrity of afferent and efferent responses and to determine the role of circulating catecholamines in newborns, 50 puppies and 24 adult dogswere studied with the use of chloralose anesthesia. Interventions were: bilateralvagotomy, bilateral carotid occlusion, central vagus stimulation, stellate stimulation, bilateral adrenalectomy, infusion of norepinephrine or isoproterenol, and intravenoustyramine. Newborns exhibited supersensitivity to exogenous norepinephrine, isoproterenol, and stellate stimulation; responses to carotid occlusion and central vagal stimulation were comparable in both groups. Newborns had less resting vagal tone. After adrenalectomy, newborns exhibited a more marked decline in systemic pressureand heart compared to adults. Myocardial catecholamine content in newborns was 1/10 that in adults, whereas plasma catecholamine concentration in newborns was 30-fold greater than in adults. These data demonstrate functional integrity of afferent and efferent cardiac autonomic pathways in the newborn, define in vivo supersensitivity to the sympathetic neurotransmitter, and suggest a dominant role of circulating catecholamines in modulation of cardiovascular events in neonates.
Effect of intravenous infusion of corticosteroids on blood pressure, electrolytes, and water metabolism in sheep
Authors: Fan JS , Coghlan JP , Denton DA , Oddie CJ , Scoggins BA , Shulkes AA
Published: December 2017

ACTH administration (80 IU/day for 5 days), which produces hypertension and charateristic metabolic effects in sheep (38), has been compared with the effect of intravenous infusion of cortisol (5 mg/h), corticosterone (0.5 mg/h), deoxycorticosterone (50 mug/h), and 11-deoxycortisol (1 mg/h), each given singly for 5 days. Further, a mixture consisting of aldosterone (3 mug/h), cortisol (5 mg/h), deoxycorticosterone (25 mug/h), corticosterone (0.5 mg/h), and 11-deoxycortisol (1 mg/h), was also infused intravenously for 5 days. In another series of experiments, 18-hydroxydeoxycorticosterone (100 mg/h) was also included in the combined-steroid solution. With the exception of 18-hydroxydeoxycorticosterone, which was not measured, the rates of infusionproduced peripheral arterial blood levels of the steroids similiar to those seen with ACTH stimulation. Blood pressure,water intake, urine output, and plasma and urinary electrolytes were measured: individual steroids had little effect on these, but manyof the metabolic changes produced by ATCH (hypokalemia and increased water intake andurine output) were produced by the combined-steroid infusion. However, the combined-steroid infusion failed to induce an increase in blood pressure similiar to that seen inthe ACTH experiments. Thus the findings are against a major role in ACTH hypertension for any steroid used, either singly or in combination. As yet unrecgnized factor/s may be involved in the ACTH-induced hypertension.
Enhanced contractility during relaxation of cat papillary muscle
Authors: Bass BG
Published: December 2017

Contractility during relaxation of isometric tension was studied in isolated, electrically driven cat papillary muscle by interpolation of test extrasystoles, all of whichpartially fused with their antecedent (control) contractions, were separated by computer from the fused contractions and then analyzed. The time course of the restitutionof contractility during relaxation was defined by plotting maximal positive dT/dt andtime-to-peak tension of the computer-separated extrasystole versus delay preceding the extrasystole. The dT/dt and time-to-peak tension, which steadily decline with progressive prematurity between contractions, both increase again during late relaxation, become progressively greater still earlier in relaxation, peak shortly after peak isometric tension, and then again decline. This phase of an apparently enhanced contractilityduring relaxation is depressed in low Ca'++ and is transmitted into the postextrasystolic period (in which it is superimposed on the usual postextrasystolic potentiation). The possible contributions of variations in series-elastic component and contractile-element lengths, actionpotential characteristics, and other factors on contractility during relaxation are discussed. It is suggested that enhanced contractility during relaxation may also be related in part to the decay of the intracellular free Ca'++ transient.
Comparative metabolism of tritiated water by macropodid marsupials
Authors: Denny MJ , Dawson TJ
Published: December 2017

The total body-water content (TBW) and rate of water turnover were measured usingtritiated water in five species of macropodod marsupials (kangaroos), which ranged in weight from 1 to 50 kg. Animals fitted with rumen cannulas were used to estimate the time required for tritiated water to equilibrate within the body of large kangaroos. In hydrated kangaroos this was 6 h, during the time 2.7% of the injected tritiated waterwas lost from the body. During dehydration, the equilibrium time was extended to 10h.Values up to 78% of body weight were found for TBW in the larger species of kangaroo, and these values were similiar to those found for other ruminantlike mammals, particularly those with a low body-fat content. The smaller macropodids had a TBW (about 60% of body weight) similiar to that of most laboratory mammals. The rates of waterturnover of the macropodids were related to body weights by the expression 1/day = 0.09kg-0.80. Macropodid marsupials have a daily water usage shich is about two-thirds ofthat found for eitherians and this may be related to the lower metabolic rate of marsupials.
Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum
Authors: Nellans HN , Frizzell RA , Schultz SG
Published: December 2017

Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum. These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current. Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes. This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport. Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline. Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels. Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process.
Enzyme secretion in the absense of zymogen granules
Authors: Rothman SS
Published: December 2017

Pure pancreatic juice was collected from the cannulated common bile duct of anesthetized rats after an overnight fast. Digestive enzyme secretion was followed in these animals during and after the progressive degranulation of acinar cells produced by sequentially applied cholinergic stimuli. The kinetics of degranulation, a progressive decrease in the number of zymogen granules in acinar cells, was estimated from the relative cell volume occupied by electron-opaque granules at various times using a random pointcount stereological technique to examine tissue sections. Three hourly injections of methacholine chloride were sufficient to produce the almost complete disappearance of electron-opaque granules from secretory cells. Greatly augmented enzyme secretion was still observed in their absence, 7-25 times greater than control values: 10-fold for protein output overall, 7-fold for trypsinogen, and 25-fold for chymotrypsinogen. Secretion in the absence of zymogen granules is discussed relativeto exocytosis and three-compartment (intracellular storage, cytoplasm, and duct lumen)secretory models.
Salt and water balance and renin activity in renal hypertension of rats
Authors: Mohring J , Mohring B , Naumann H-J , Philippi A , Homsy E , Orth H , Dauda G , Kazda S
Published: December 2017

In male Sprague-Dawley rats, renal artery constriction in the presence of an inact contralateral kidney induced sodium retention (for 2-3 wk), moderate potassium loss,elevation of blood volume (BV), and an increase in water turnover. It is suggestedthat renal artery constriction activates the renin-angiotensin-aldosterone system, resulting in disordered regulation of salt and water balance and in blood pressure (BP) elevation. Subsequently, sodium balance was reestablished in one group of hypertensive rats. The previously retained sodium was kept in the body, and BV and reninactivity remained elevated. In a second group of animals, a malignant course of hypertension developed: BP surpassed a critical level of about 180 mmHg; sodium, potassium, and water were lost; BV declined; renin activity was further stimulated; and in the contralateral kidney malignant nephrosclerosis occurred. It is assumed that pressure diuresis and natriuresis induce a vicious circle: the increasing renin activity may maintain or further increase BP level, therby inducing further salt and water loss, etc.; high BP levels and high renin activities induce vascular damage and deterioration of renal function.
Hydraulic and oncotic pressure measurements in inner medulla of mammalian kidney
Authors: Sanjana VM , Johnston PA , Deen WM , Robertson CR , Brenner BM , Jamison RL
Published: December 2017

The vasa recta are thought to play an important role in the transfer of water andsolutes within the renal medulla. Hydraulic pressures were measured in vasa recta onthe surface of the exposed papilla in young Munich Wistar rats, and blood was collected from these microvessels for determination of total protein concentration and calculation of colloid oncotic pressure. In descending vasa recta at the base of the exposed papilla, mean hydraulic pressure was 9.2 plus or minus 0.4 (SE) mmHg and plasma protein concentration averaged 7.1 plus or minus 0.4 g/100 ml. Corresponding valuesin ascending vasa recta at the same level were 7.8 plus or minus 0.4 mmHg and 5.6 plusor minus 0.3 g/100 ml. respectively. The protein concentrations correspond to calculated oncotic pressures of 26 and 18 mmHg in descending and ascending vasa recta, respectively. We interpret these findings as evidence for net water uptake by the vasa recta in the renal inner medulla for which the driving forces are the transcapillary hydraulic and oncotic pressure differences.
Substrate utilization and oxygen consumption by canine jejunal mucosa in vitro
Authors: Lester RG , Grim E
Published: December 2017

Oxygen consumption, carbon dioxide production, and substrate utilization by small pieces of canine jejunal mucosa have been measured in vitro. In the absence of added substrate, the Qo2 was 0.21 mumol/h per mg dry wt and the respiratory quotient (RQ) was 0.73 indicating the endogenous substrate to be lipid in nature. When glucose or galactose was added, Qo2 and RQ increased. Metabolism of the endogenous substrate was depressed by fructose but not by glucose or galactose. Less than 15% of the metabolized glucose and fructose was degraded to Co2; 80% of the metabolized glucose was recovered as lactate. Galactose disappeared at one-seventh the rate of glucose, but 40% of that metabolized was degrated to CO2. In all experiments Qo2 showed marked cyclic fluctuations with an amplitude of 30-40% of the mean value and a period of 30-40 min. For tissues from a single animal, the cycles were in phase on a clock time basis, indicating that the cycles were synchronized by some in vivo mechanism.
Angiotensin and the hemodynamics of chronic salt deprivation
Authors: Coleman TG , Cowley AW  , Guyton AC
Published: December 2017

Salt deprivation has been shown to cause fluid volume contraction and marked renin release; it is not clear whether angiotensin-induced vasoconstriction adds to low volume in compromising circulatory function or whether there are additional facets to the salt-deprived state. Mature Wistar rats were fed a low-salt diet for 1 mo and then, under pentobarbital anesthesia, compared to normals. Arterial pressure (is congruent to 125 mmHg), cardiac output (is congruent to 200 ml/min per kg), and total peripheral resistance were nearly identical in both groups. The influence of angiotensin was estimated by injecting converting enzyme inhibitor (SQ 20881, 1 mg/kg), and then observing the immediate hemodynamic response. Salt-deprived rats responded with a large (-47 mmHg) fall in pressure and total peripheral resistance indicating that, although total peripheral resistance was normal in salt deprivation, an increased fraction (30% vs. 11%) of the resistance was supported by angiotensin. Cardiac output decreased (-8%) in contrast to the increase that would be expected during marked arterial dilation; elevated angiotensin levels may have caused a moderate, beneficial decrease in venous compliance. These results suggest that circulatory function is adequately maintained during salt deprivation by a combination of normal total peripheral resistance and decreased venous compliance.
Neutral amino acid transport pathways in uptake of L-thyroxine by Ehrlich ascites cells
Authors: Stitzer LK , Jacquez JA
Published: December 2017

Neutral amino acid pathways were investigated as possible mediators of L-thyroxine (T4) entry into ascites cells. 14C-Labeled T4, alpha-aminoisobutyric acid (AIB), L-phenylalanine (Phe), and cycloleucine (cLeu) uptakes were measured at initial extracellular amino acid concentrations of 1 muM in a modified Krebs-Ringer phosphate buffer, pH 7.4. T4 uptake was markedly slower than that of AIB, Phe, or cLeu over a 25-min period. T4 uptake was neither competitively stimulated nor inhibited by either AIB or Phe when these latter amino acids were varied over the concentration range 1.0 x 10(-6) to 1.0 x 10(-2) M. Preloading cells with 30 mM L-methionine did not enhance the uptake of T4. TJ efflux from preloaded cells was not affected by either AIB or Phe in the extracellular fluid (ECF). The uptakes of AIB, Phe, and cLeu were markedly altered by replacement of ECF Na+ with choline+, whereas T4 uptake was unchanged. It was concluded that neural amino acid transport pathways (specifically A, L, ASC, and beta) do not participate in the transmembrane transfer of L-thyroxine into Ehrlich ascites cells.
High K+ effects on PAH transport and permeabilities in isolated snake renal tubules
Authors: Dantzler WH , Bentley SK
Published: December 2017

Effects of high potassium concentrations on para-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Increasing the potassium concentration in bath from 3 mM TO 10 mM OR 40 MM led to about 50% decrease in net PAH transport from bath to lumen in less than 10 min, but transport still occurred against concentration gradient. Cell water PAH concentration was not significantly depressed in 10 mMpotassium and was nearly double control level in 40 mM potassium. Apparent luminal membrane permeability to PAH, calculated from perfusion studies, averaged about 3.5 x 10(-5) cm sec(-1) in 3 mM potassium, 1.15 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.48 x 10(-5) cm sec(-1) in 40 mM potassium. Apparent peritubular membrane permeability, determined from PAH efflux from tubules with oil-filled lumens averaged about 0.5 x 10(-5) cm sec(-1) in 3 mM potassium, 0.29 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.17 x 10(-5) cm sec(-1) in 40 mM potassium. These data suggest that high potassium concentrations depress transepithelial PAH transport primarily by reducing luminal and peritubular membrane permeabilities. Effect of high potassium on PAH transport was reversed within 20 min after restoration of control potassium concentration.
A phylogenetic study of the role of cyclic AMP in lipid synthesis in vertebrates
Authors: Bricker LA , Marraccini LA
Published: December 2017

The effect of cyclic AMP on the incorporation of acetate-2-14C into sterols and fatty acid in vitro in slices of liver and intestine was examined in various representatives of the vertebrate group. In no instance was an effect on lipid synthesis noted in intestine. Cyclic AMP exerted no significant effects on hepatic lipogenesis in lower vertebrates, including the nurse shark, catfish, toad, or iguana. However, the nucleotide strongly inhibited the incorporation of acetate-2-14C into fatty acid by the chicken liver. Similar inhibition of fatty acid synthesis was also noted in rat liver, but in this mammalian species hepatic sterol synthesis was also strikingly suppressed by cyclic AMP. Interruption of the enterohepatic circuit in the rat, while enhancing rates of sterol synthesis in both liver and intestine, neither enhanced nor diminished hepatic susceptibility to suppressed sterologenesis by cyclic AMP, nor did it confer on the intestine any newfound capacity for cyclic AMP-regulated lipid synthesis.
Frequency responses of down- and guard-hair receptors in the cat
Authors: Hahn JF , Wall JT
Published: December 2017

In the saphenous nerve of the barbiturate-anesthetized cat, single-unit recordings were made while stimulating guard-hair of down-hair receptors with sinusoidal or narrow-band "noise" displacements. From the units' frequency responses it was inferred that a significant contribution to their firing rate is made by stimulus displacement as well as by stimulus velocity. The appellation "velocity detector" for these units is only partially correct. The proposed division of guard-hair units into types G1 and G2 was not supported by the results obtained with the stimulus used in this investigation.
Cardiac lymph flow and composition in acute myocardial ischemia in dogs
Authors: Feola M , Glick G
Published: December 2017

Cardiac lymph was obtained from 12 normal dogs (group 1) for two consecutive 2-h control periods and from 7 dogs (group 2) for 2 h before and 2 h after occlusion of the circumflex branch of the left coronary artery. Lymph composition was studied with reference to pH, red blood cell (RBC) concentration, total protein content, potassium and sodium ion concentrations, and creatine phosphokinase (CPK) and acid phosphatase enzyme activities. No significant difference was noted in any variable between the two groups during the firts 2-h period. In group 1, no significant changes occurred in any variable as a result of the passage of time alone. In group 2, 2 h of myocardial ischemia produced increases of 53.3 plus or minus 5.1% in lymph flow, 67 plus or minus 5% in protein content, and 418 plus or minus 27% in the RBC concentration, suggesting increased blood capillary permeability. Lactate rose 120.5 plus or minus 27%, potassium concentration increased 16.9 plus or minus 2.4%, acid phosphatase increased 30 plus or minus 3%, and CPK rose 61.6 pluse or minus 10.9%, suggesting ischemic injury of myocardial cells. These changes in lymph were statistically significant (P LESS THAN 0.05) and reflect both capillary and myocardial cell abnormalities.
Influence of altered O2 tension on substrate metabolism in perfused rat lung
Authors: Rhoades RA , Shaw ME , Eskew ML
Published: December 2017

Effects of hypoxia (1.5 h) on glucose and palmitate metabolism were investigated in perfused lungs from normal rats and rats exposed for 24 h to hypobaric conditions (simulated altitude of 24,000 ft). Hypoxic lungs were ventilated with 5% O2-5% CO2 and control lungs with 21% O2-5% CO2. Blood gases and pH remained stable during the 1.5-h perfusion period. Exposure of normal rat lungs to 1.5 h of in vitro hypoxia (blood Po2=34 mmHg) significantly increased lactate production and mean arterial pulmonary pressure, but did not alter glucose uptake, pyruvate levels, and oxidation of either [U-14C]glucose or [1-14C]palmitate to CO2. Incorporation of labeled glucose and palmitate into lung lipids was also unaltered. In contrast to normal lungs, prior exposure to hypoxia for 24 h and subsequent perfusion under hypoxic conditions significantly stimulated glucose uptake (74% increase), markedly increased glucose incorporation into lung lipids, and increased oxidation of glucose to CO2. Lactate/pyruvate ratios also showed a significant 38% increase. Lung glycogen was unchanged following 24 h hypoxia. These data indicate that adaptive changes occur in metabolic processes within the lung during acute changes in O2 tension.
Contractile inactivation in frog single denervated muscle fibers
Authors: Stuesse SC , Lindley BD
Published: December 2017

After preliminary conditioning depolarizations, single muscle fibers of the frog were tested for ability to contract in response to depolarization by 100 mM K+ Ringer solution. Denervated fibers (6-42 days) lose their ability to produce a 100 mM K+ contracture more rapidly than do control fibers. This decrease in 100 mM K+ contracture size (inactivation) is dependent on length of exposure to and magnitude of the conditioning depolarization and on the calcium concentration in the external medium. At 0.4 mM Ca++, the inactivation is 3 times faster than at 1.5 mM Ca++. The rate of contracture loss is not correlated with fiber diameter or the number of days after failure of neuromuscular transmission, and the preliminary conditioning depolarizations do not affect the rate of terminal relaxation from the 100 mM K+ contractures.
Responses to cold in the midbrain sonar center of hibernating and tropical bats
Authors: Howell DJ , Simmons J , Horst R
Published: December 2017

The central gray matter of the bat midbrain, when electrically stimulated, causes the animal to produce a string of species-specific biosonar cries. Changes in this response with progressive cooling were studied in tropical homeothermic bats and in temperate hibernating bats. The species of hibernators chosen often move between hibernacula in the winter, flying and echolocating at low body temperatures (Tb). It was found that the midbrain "sonar center" exhibits a differential response to cooling that depends on the thermal propensities of the animal and its natural environment. Tropical bats followed a Q10 similar to that reported for other nonhibernating mammals and ceased responding at Tb 14-15 degrees C. Temperate zone-hibernating bat brains showed a relative insensitivity to temperature change and still responded at Tb 4-5 degrees C. Individual sonar cries within a string showed that duration was correlated with temperature but amplitude was unaffected. The study provides data for the functional separation of some parameters of biosonar and gives further evidence for differential nervous function in eurythermal versus stenothermal animals.
Potassium adaptation and Na-K-ATPase activity in mucosa of colon
Authors: Silva P , Charney AN , Epstein FH
Published: December 2017

The specific activity of sodium-potassium-activated adenosine triphosphatase in the mucosa of the colon rises when the dietary load of potassium is increased. The change in enzymatic activity depends on the presence of intact adrenal glands, since adrenalectomy abolishes the response of Na-K-ATPase to potassium loading. The increased secretory rate of aldosterone normally evoked by potassium loading appears to mediate at least in part of the effect of potassium loading, since aldosterone induces a discernible increase in the specific activity of Na-K-ATPase in the colon of adrenalectomized rats.
Difference between endocardial and epicardial utilization of glycogen in the ischemic heart
Authors: Ichihara K , Abiko Y
Published: December 2017

In the nonischemic canine left ventricle, levels of glycogen, glucose-6-phosphate (G6P), and lactate, and phosphorylase activity in the endocardial layers were higher than those in the epicardial layers, but the phosphocreatine (PCr) level in the endocardial layers was lower than that in the epicardial layers, and there were no differences in the adenosine triphosphate (ATP) level between the endo- and epicardial layers. Upon ligation of a small branch of the left descending coronary artery, levels of glycogen and PCr decreased, while those of G6P and lactate increased, and the activity of phosphorylase increased. The level of ATP was not affected by the coronary ligation. Thus the coronary ligation accelerated the glycogenolysis and glycolysis in the myocardium without affecting ATP level, and the acceleration in metabolism in the endocardial layers was more rapid and marked than that in the epicardial layers.
Absence of estimated glomerular pressure autoregulation during interrupted distal delivery
Authors: Navar LG , Chomdej B , Bell PD
Published: December 2017

Micropuncture studies in dogs have suggested that a distal tubule-to-afferent arteriole feedback system may participate in the autoregulation mechanism at the single-nephron level. To evaluate the effect of interrupted distal delivery on glomerular capillary pressure (GP) and its autoregulation, the proximal tubule was blocked with oil and maximal stop-flow pressure was measured with a micropressure servo-null system. The GP was estimated from the sum of stop-flow pressure and the plasma colloid osmotic pressure (membrane oncometer). In 18 dogs given a mild mannitol load, average +/- SD control arterial pressure was 118 +/- 16 mmHg, proximal tubule pressure was 24 +/- 5 mmHg, and estimated GP averaged 70 +/- 10 mmHg. There was a highly significant relationship between estimated GP and arterial blood pressure. Similar results were obtained in hydropenic dogs. In response to decreases in renal arterial pressure in individual dogs, stop-flow pressure and estimated GP failed to exhibit autoregulation although autoregulation of renal blood flow, GFR, and proximal tubule pressure was observed over an arterial pressure range of 150-95 mmHg. These results indicate that interruption of normal distal delivery by proximal tubule blockage interferes with the ability of the nephron to autoregulate glomerular pressure. They provide further evidence in support of the concept that a distal tubular feedback mechanism participates, at least in part, in the autoregulatory control of glomerular pressure.
Stimulation of intestinal smooth muscle by atropine, procaine, and tetrodotoxin
Authors: Bortoff A , Muller R
Published: December 2017

In order to determine whether or not atropine, procaine, and tetrodotoxin (TTX) can stimulate intestinal smooth muscle directly, we examined the effects of these drugs on the mechanical and electrical activities of several types of cat intestinal smooth muscle preparations. The preparations consisted of isolated rings of 1) intact intestinal wall, 2) intact longitudinal and circular muscle, 3) ganglion-free circular muscle, and 4) ganglion-free circular muscle devoid of its dense layer and plexus muscularis profundus. Atropine and procaine (greater than 10(-4) M) stimulated all four types of preparation. On the other hand, TTX (up to 5 X 10(-6) M) stimulated only preparations 1 and 2. It is concluded that whereas atropine and procaine can directly stimulate intestinal smooth muscle, the excitatory effect of TTX is neurally mediated.
Skeletal buffering of acute metabolic acidosis
Authors: Bettice JA , Gamble JL
Published: December 2017

Decreases in the sodium content of bone were measured to evaluate the role of this tissue in the buffering of acute metabolic acidosis. The bones of rats and dogs were labeled with radiosodium prior to the infusion of HCl, and changes in the radioactivity were used to indicate the loss of bone sodium. Significant reductions in the skeletal sodium occurred within the first 5 h of acidosis, and these losses can only be partially attributed to the hyponatremia accompanying the acid infusion. Decreases were greatest in the smaller bones of the rat; and, in the dog, the losses from flat bones exceeded those of the long bones. Only the rapidly exchangeable sodium of bone was involved in the changes due to acidosis. Soft tissue buffering may be more important initially; during 1.5-h experiments, the skeletal losses were small and could be ascribed almost entirely to the decrease in the amount of sodium contained in bone water. However, at the end of 5.0 h, the quantity of sodium released from the skeleton is sufficient to account for much of the tissue buffering.
In vitro measurement of margin of safety of neuromuscular transmission
Authors: Waud DR , Waud BE
Published: December 2017

The margin of safety of neuromuscular transmission was measured in isolated guinea pig lumbrical muscles. Twitch height of an indirectly stimulated muscle was reduced stepwise by suitable concentrations of tubocurarine for comparison with the associated occlusion of receptors by the drug. Receptor occlusion was estimated from the effect of tubocurarine on carbachol depolarization measured extracellularly by the moving-fluid electrode technique. Roughly 75-80% of the receptor pool had to be blocked before the twitch height began to fall, and 90-95% had to be blocked before the twitch response was completely abolished. These results agree well with those found previously in vivo. Thus, the present results add further support to the earlier measurements. In particular, artifacts that might have been present because of the complex pharmacokinetic situation in vivo have been ruled out.
Characteristics of urate influx in the rat nephron
Authors: Kramp RA , Lenoir RH
Published: December 2017

Permeability of the tubular epithelium to urate presented on the peritubular side was studied in anesthetized rats during mannitol diuresis by capillary microinjections of [14C]urate and [3H]inulin, [14C]PAH and [3H]inulin, or [14C]urate and [3H]PAH. Recovery of isotopes was determined in urine collected serially from the injected and contralateral kidney. Appearance and peak excretion of urate in the experimental but not in the contralateral kidney preceded inulin and coincided with PAH, indicating proximal permeability to urate. Recovery of urate was higher from the injected than from the contralateral kidney. Urate precession and recovery did not change after addition of PAH (1.5-6.4 mm) to [14C]urate-[3H]inulin solutions, whereas they decreased significantly in the experimental kidney after pyrazinoate (1.6-3.2 mM) addition. On the other hand, no effect of urate on [14C]PAH-[3H]inulin injections was detectable. These findings are suggestive of a carrier-mediated transtubular influx of urate in rat proximal tubule. Absence of competition with PAH may suggest differences in the secretory mechanisms for organic acids.
Hepatic metabolism of genetically diabetic (db/db) mice. I. Carbohydrate metabolism
Authors: Chan TM , Young KM , Hutson NJ , Brumley FT , Exton JH
Published: December 2017

Hepatic carbohydrate metabolism in genetically diabetic mice (db/db) and their normal littermates has been studied. In db/db mice, body water was below normal and declined with age. The liver of db/db mice was abnormally large in relation to the metabolic mass of the body at all ages studied. In db/db mice, hepatic glycogenolysis, glycogen synthesis, glycogen synthetase, and phosphorylase were markedly increased. Gluconeogenesis from alanine or lactate in perfused livers of db/db mice was greater than normal per 100 g body water. Activities of fructose-1, 6-biophosphatase, glucose-6-phosphatase, glucokinase + hexokinase, and pyruvate kinase were elevated in livers of db/db mice. Diabetic mouse livers perfused with lactate showed a markedly reduced concentration of P-enolpyruvate and clear "forward crossover" between fructose-1, 6-P2 and fructose-6-P. In vivo glucose clearance, measured with [3-3H]glucose, in db/db mice was 170% that of normal mice. Data presented indicate that in livers of db/db mice: 1) glucose production is elevated prior to hyperglycemia, 2) glycogen turns over more rapidly, and 3) glycolytic and gluconeogenic enzymes are elevated paradoxically. These abnormalities are discussed from the viewpoint of their etiology.
Restriction of hepatic gluconeogenesis and ureogenesis from threonine when at low concentrations
Authors: Bloxam DL
Published: December 2017

Experiments were carried out with the isolated perfused liver of the overnight-starved rat to study the control of the conversion of the essential amino acid threonine to glucose and urea from the point of view of its conservation when in short supply. The relationships between the concentration of added L-threonine and the rate of glucose and urea production showed that both pathways have considerable capacity and were saturated at a high (15 mM) concentration of threonine. However, these concentration-rate relationships were sigmoidal, so that at low concentrations the rates of conversion were disproportionately low. Thus at physiologic levels of threonine, no measurable stimulation of glucose or urea output was observed. Hepatic uptake of threonine was similarly disproportionately reduced at near-physiologic levels. Glucagon stimulated glucose and urea outputs in parallel fashion and stimulated the uptake and inward membrane transport of threonine at both saturating and low concentrations. This and the changes in intracellular and extracellular concentrations of threonine indicate the transport is rate limiting for both pathways. If this is so, the apparent restrictive property probably resides at the plasma membrane. Since the liver is the end point of threonine metabolism, this property would effectively limit the utilization of threonine when in short supply.
Effect of acetylcholine on automaticity of canine Purkinje fibers
Authors: Tse WW , Han J , Yoon MS
Published: December 2017

The effect of acetylcholine on automaticity of Purkinje fibers was studied in isolated canine false tendon preparations with conventional microelectrode techniques. Of 15 preparations with the control spontaneous rate of 12-60 beats/min, acetylcholine in a concentration of 0.5 mug/ml decreased the spontaneous rate by 20-87% in 13 preparations. This decrease in automaticity was due to a decrease in the slope of phase 4 depolarization and an increase in the maximum diastolic potential. The inhibitory effect of acetylcholine could be reversed by atropine in a concentration of 3 mug/ml in six preparations and prevented by pretreatment with atropine in another six preparations. Atropine per se did not have any appreciable effect on automaticity of Purkinje fibers. The results indicate that acetylcholine significantly suppresses automaticity of canine Purkinje fibers through its muscarinic action.
Insulin removal by isolated perfused rat liver
Authors: Misbin RI , Merimee TJ , Lowenstein JM
Published: December 2017

Removal of unlabeled insulin was studied in the perfused rat liver. Insulin removal followed first-order kinetics over the range of concentrations found in the portal vein of postabsorptive rats, but deviated from first-order kinetics in experiments with a wider concentration range. Clearance was more than twice as great at concentrations normally found in the portal vein in the postabsorptive state (0.40-1.1nM or about 60-100 muU/ml) than at concentrations expected after pancreatic stimulation (4.5-7.0 nM). Saturation of the liver's capacity to remove insulin, however, was not observed even at higher levels. Insulin clearance diminished when the flow rate was reduced. It was not significantly altered by prolonged starvation. Our results suggest that when the insulin concentration is high a greater percentage escapes hepatic degradation then when it is low. Hepatic insulin clearance is in part dependent on the portal flow rate. The kinetics of insulin removal by the perfused liver cannot be accounted for by the properties of insulin-degrading enzymes described by others.