bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of bombesin and related peptides on the release and action of intestinal hormones on pancreatic secretion.
Authors: Konturek S J , Król R , Tasler J
Published: December 2014

1. Pancreatic volume flow as well as bicarbonate and protein secretion from pancreatic fistulas have been measured in response to i.v. infusion of graded doses of bombesin and related peptides containing the COOH‐terminal fragment of the bombesin molecule in conscious dogs with intact antrum and in anaesthetized animals with antrectomy, or antrectomy and enterectomy. 2. Bombesin and related peptides given to conscious dogs produced a potent and dose‐dependent increase in pancreatic protein output reaching a maximum equal to that induced by the octapeptide of cholecystokinin (OP‐CCK) as well as a small rise in bicarbonate output attaining a peak amounting to about 10% of that evoked by secretin. The serum gastrin level rose progressively during the infusion of bombesin to reach a peak with the highest dose of peptide. 3. Bombesin infused i.v. in anaesthetized animals with resected antrum also evoked a marked increase in pancreatic protein secretion without significant changes in the serum gastrin level. Following the removal of the antrum and small intestine, bombesin failed to show any stimulation of the pancreatic secretion or any change in the serum gastrin level. It is concluded that the strong stimulatory action of bombesin and related peptides on pancreatic secretion cannot be entirely ascribed to the release of gastrin but might be attributed at least in part to the release of intestinal hormones, particularly CCK. 4. Atropine and the growth hormone‐release inhibiting hormone (GH‐RIH), which were shown to inhibit the release of CCK induced by duodenal perfusion of an amino acid mixture, also caused the inhibition of pancreatic protein secretion by bombesin but failed to affect the pancreatic response to OP‐CCK. The results indicate that bombesin releases, in addition to gastrin, CCK from the gut by a mechanism largely dependent upon cholingeric innervation.
Active sodium uptake by the skin of foetal sheep and pigs.
Authors: France V M
Published: December 2014

1. Simultaneous measurements of unidirectional sodium fluxes across foetal skin incubated in vitro with identical solutions ([Na] = 150 mM) bathing either side showed a flux ratio (influx/efflux) of 1‐40+/‐0‐08 in twenty‐seven sheep skins, which was significantly different from unity (P less than 0‐001). The gestational ages ranged from 47 to 98 days (term = 147 days). Similar experiments on eight foetal pig skins at 58 days gestation (term = 114‐118 days) gave a mean flux ratio of 1‐10 +/‐ 0‐03 (P less than 0‐02). 2. Unidirectional sodium fluxes measured with dilute Ringer solution on the outside (mucosal) surface ([Na]0 = 100mM) gave influx to efflux ratios of 0‐86 +/‐ 0‐09 in seventeen sheep (P less than 0‐05) and 1‐07 +/‐ 0‐26 in five foetal pigs; the value predicted for passive movement was 0‐67. 3. Incubation with inhibitors, ouabain (10‐4 M) or dinitrophenol (DNP) (10‐4 M) gave a flux ratio for sodium which was not significantly different from unity in the absence of a gradient, or from 0‐67 when the concentration gradient was applied. 4. Sequential measurement of unidirectional diffusional fluxes of tritiated water across foetal skin gave flux ratios of 0‐98 +/‐ 0‐02 in six sheep skins and 1‐06 +/‐ 0‐11 for four pig skins in control conditions. When the outside solution was diluted to give an osmotic gradient of 100 m‐osmole. kg‐1 across the skin a flux ratio of 0‐95 +/‐ 0‐07 was obtained for seven sheep and was not measured in pig skin. Hormones and inhibitors had no effect on the diffusional flux ratio for water in the presence or absence of an osmotic gradient. 5. Lysine vasopressin (ADH) (200 mu./ml.) increased influx and efflux of water in the presence and, to a lesser extent in the absence of an osmotic gradient in sheep skin. In pig skin prolactin (1 u./ml.) increased both influx and efflux, but ADH had no effect on diffusional water fluxes. 6. ADH increased sodium influx in sheep skin slightly but vasotocin (5‐5 mu./ml.) was more potent, particularly in the presence of an opposing diffusion gradient. Vasotocin (55 mu./ml.) reduced sodium influx in pig skin ADH had no effect on influx or efflux and prolactin reduced sodium influx and efflux. Ouabain and DNP generally reduced permeability to both sodium and water in sheep skin but had no effect in pig skin.
Dynamic properties of the responses of single neurones in the cochlear nucleus of the rat.
Authors: Moller A R
Published: December 2014

1. The dynamic properties of unit responses to amplitude‐modulated tones were studied using modulation with pseudorandom noise and described by cross‐covariance and integrated cross‐covariance functions between the discharge rate and the modulation. Under the experimental conditions used, these two functions are valid approximations of the system's impulse and step response functions respectively. 2. On the basis of their impulse response functions units could be classified into two groups, Type I with a low adaptation and Type II with a large degree of adaptation as well as a damped oscillation in their impulse response functions. 3. The response pattern of the Type II units is most likely the result of a negative feed‐back striving to keep the discharge rate at a nearly constant level. 4. The cross‐covariance functions are shown to remain unchanged during long duration recordings from the same unit.
Blood pressure and sleep in the rat in normotension and in neurogenic hypertension.
Authors: Junqeira F L , Krieger E M
Published: December 2014

1. Blood pressure was recorded in normotensive rats (114 +/‐ 2 mmHg) and in those made hypertensive by baroreceptor denervation (135 +/‐ 4 mmHg) during natural sleep. The different states of the wakefulness‐sleep cycle were identified by analysis of the frontal electrocorticogram, the cervical electromyogram and by behavioural changes. 2. During synchronized sleep the arterial pressure in the control animals usually remained unchanged as compared to values prevailing when the rats were awake and quiet. The blood pressure usually attained higher levels in the sino‐aortically denervated rats during this state. 3. Coincidently with the short episodes of electrocortical desynchronization of the synchronized sleep the blood pressure exhibited rapid oscillations. These fluctuations were greater in the rats with neurogenic hypertension where there were large pressure drops. 4. During desynchronized (REM) sleep arterial pressure underwent marked oscillations. While in the control rats the pressure usually rose, the baroreceptor‐denervated rats showed a severe reduction in pressure. Arterial pressure in denervated animals became lower than that of the control rats, 106 +/‐ 2 and 121 +/‐ 2 mmHg, respectively. 5. We interpret these results to mean that in the rat alterations in the sensitivity of the baroreceptor reflex could be an important factor in preventing the arterial pressure from rising to hypertensive levels during syndhronized sleep and from dropping to low values during desynchronized (REM) sleep.
The oxidation of glucose, ketone bodies and acetate by the brain of normal and ketonaemic sheep.
Authors: Lindsay D B , Setchell B P
Published: December 2014

1. The utilization and oxidation of glucose, acetate and ketone bodies by the brain of sheep has been determined from measurements of arteriovenous (A‐V) differences and cerebral blood flow, as well as by infusing 14C‐labelled metabolites. 2. The A‐V difference for glucose was generally more than one sixth, on a molar basis, that of oxygen. 3. The mean rate of glucose utilization by the brain of conscious sheep (0‐508 +/‐ 0‐063 mumole/g per minute) was maintained even when the capillary glucose concentration was below 1‐4 mM. 4. The amount of 14CO2 produced from [U‐14C]glucose by the brain was consistent with glucose being the only energy source for the brain, even during hypoglycaemia and hyperketonaemia. 5. There was no appreciable production of lactate or pyruvate by the brain. 6. There was no significant A‐V difference for acetate across the brain in normal or undernourished pregnant sheep. The small A‐V differences that were measured show that less than 5% of the CO2 produced could be derived from acetate, a conclusion that is supported by experiments using [U‐14C]acetate. 7. No significant A‐V difference was detectable across the brain for 3‐hydroxybutyrate or acetoacetate in normal fed, pregnant ketonaemic or even anaesthetized sheep infused with acetoacetate. Experiments in which [U‐14C]‐D(‐)‐3‐hydroxybutyrate was infused also showed that less than 5% of CO2 was derived from ketone bodies. 8. In anaesthetized sheep infused with acetoacetate, measurements were made simultaneously across brain, heart and skeletal muscle. In contrast to the non‐significant uptake of ketone bodies by the brain, uptake by heart and skeletal muscle was sufficient to account for nearly 60% of their oxygen consumption. 9. Experiments using [14C]hydroxybutyrate confirmed that during infusion of acetoacetate most of the CO2 produced by the heart, but not by the brain, was derived from ketone bodies. 10. In anaesthetized sheep ketone bodies penetrate only slowly into cerebrospinal fluid. 11. It is proposed that mechanisms for the utilization of ketones by the sheep brain have not evolved because glucose utilization by the brain is a smaller fraction of whole body glucose utilization than in man and rats.
The effect of dopamine on neurohypophysial hormone release in vivo and from the rat neural lobe and hypothalamus in vitro.
Authors: Bridges T E , Hillhouse E W , Jones M T
Published: December 2014

1. The rat hypothalamus (containing the supra‐optic nuclei, paraventricular nuclei, median eminence and proximal pituitary stalk) has been incubated in vitro and shown to be capable of releasing the neurohypophysial hormones, oxytocin and arginine vasopressin, at a steady basal rate about one twentieth that of the rat neural lobe superfused in vitro. 2. The hypothalamus and neural lobe in vitro released both hormones in a similar arginine vasopressin/oxytocin ratio of about 1‐2:1. However, when release was expressed relative to tissue hormone content, the hypothalamus was shown to release about three times as much arginine vasopressin and six times as much oxytocin as the neural lobe. 3. Dopamine in a concentration range of 10(‐3)‐10(‐9)M caused graded increases in hormone release from the hypothalamus in vitro to a maximum fivefold increase over preceding basal levels. The demonstration that apomorphine also stimulated hormone release whereas noradrenaline was relatively ineffective suggested that a specific dopamine receptor was involved. A separate cholinergic component in the release process was indicated by the finding that acetylcholine stimulated release to a maximum fivefold increase in concentrations of 10(‐3)‐10(‐9)M. 4. The fact that the isolated hypothalamus can be stimulated by dopamine and acetylcholine to release increased amount of oxytocin and arginine vasopressin raises the question of the origin and fate of the hormones released in this way. The possibility that they could be released into the hypophysial portal circulation from median eminence to affect the anterior lobe of the pituitary is discussed. 5. In similar doses, both dopamine and noradrenaline injected into the lateral cerebral ventricles of the brain of the anaesthetized, hydrated, lactating rat caused the release of arginine vasopressin and oxytocin. Apomorphine release both hormones but at a higher dose level and to less effect than the catecholamines. 6. The hormone release induced in vivo by dopamine could be prevented by the prior administration of haloperidol or phentolamine and these antagonists were equally effective in blocking the hormone release due to noradrenaline. The involvement of a specific dopamine receptor was more clearly implicated by the use of pimozide which completely inhibited the hormone release due to dopamine and apomorphine but not that due to noradrenaline. 7. It is suggested that the release of neurohypophysial hormones can be stimulated via a dopaminergic nervous pathway in addition to a cholinergic one. The possibility that the osmoreceptor mechanism for the release of antidiuretic hormone from the neural lobe of the pituitary may involve such a dopaminergic pathway is discussed.
Distribution of fusimotor axons to intrafusal muscle fibres in cat tenuissimus spindles as determined by the glycogen‐depletion method.
Authors: Barker D , Emonet-Dénand F , Harker D W , Jami L , Laporte Y
Published: December 2014

1. The distribution of fusimotor axons to bag1, bag2 and chain muscle fibres in cat tenuissimus spindles has been studied using a modification of the glycogen‐depletion technique of Edstrrom & Kugelberg (1968). Single fusimotor axons were stimulated intermittently at 40‐100/sec for long periods (30‐90 sec) during blood occlusion. Portions of muscle containing the activated spindles were quick‐frozen, fixed in absolute ethanol during freeze‐substitution, and then embedded in paraffin wax. Serial transverse sections were stained for glycogen using the periodic acid‐Schiff method, and examined for depletion. 2. Dynamic gamma axons (i.e. those that increase the dynamic index of primary‐ending responses to ramp stretches of large amplitude) depleted bag1 fibres almost exclusively. 3. Static gamma axons (i.e. those that reduce or abolish the dynamic index) depleted both bag and chain fibres. Bag1 and bag2 fibres were depleted about equally. 4. A single static gamma axon may activate both bag and chain fibres in one spindle (the most common pattern), chain fibres only in another, and bag fibres only in a third spindle. 5. Static gamma axons with conduction velocities less than 25 m/sec also had a non‐selective distribution, but no depletion was observed in bag2 fibres. 6. The zones of depletion produced by dynamic gamma axons were distributed more or less equally in the intra‐ and extracapsular parts of spindle poles, whereas those produced by static gamma axons were mainly intracapsular. 7. The results are compared with the glycogen‐depletion studies of Brown & Butler (1973, 1975) and our own study of the distribution of static gamma axons to spindles in which all other motor axons had degenerated (Barker, Emonet‐Dénand, Laporte, Proske & Stacey, 1973). The implications of the finding that both static gamma and dynamic gamma axons activate bag1 fibres are discussed.
Quantitative analysis of retinal ganglion cell classifications.
Authors: Hochstein S , Shapley R M
Published: December 2014

The classification of cat retinal ganglion cells as X or Y on the basis of linearity or nonlinearity of spatial summation has been confirmed and extended. Recordings were taken from optic tract fibres of anaesthetized, paralysed cats. 2. When an alternating phase sine wave grating was used as a stimulus, X cells had null positions and Y cells responded at all positions of the grating. 3. These results did not depend on the temporal wave form or the temporal frequency of pattern alternation over a wide range. 4. At high spatial frequencies for the particular cell, a Y cell gave abig 'on‐off' response, or frequency doubling, at all positions of the grating, while an X cell did not. 5. The use of contrast sensitivity versus spatial phase also served to differentiate the two cell types. With an alternating sine grating stimulus X cells had a sinusoidal dependence on spatial phase, while each Y cell's sensitivity depended in a complicated manner on spatial phase. 6. Sensitivity versus spatial phase for different Fourier components of the neural response also separated the two classes of cells. Significant second harmonic distortion was present in Y cells. The second harmonic component was spatial phase insensitive, and became dominant at high spatial frequencies. 7. The maximum of the 2nd/1st harmonic ratio was taken as an index of nonlinearity. X cells always had a nonlinearity index less than 1 while in Y cells this index always exceeded 1. 8. Response to spots, diffuse light and drifting gratings were compared to the nonlinearity index as a basis for classifying cells. The nonlinearity index was most reliable because it was least dependent on retinal eccentricity.
Spatial properties of horizontal cell responses in the turtle retina.
Authors: Lamb T D
Published: December 2014

1. Intracellular recordings were made from horizontal cells in the retina of the turtle Pseudemys scripta elegans. Spatial properties of the responses were determined using brief flashes of monochromatic light. 2. For a light stimulus in the form of a long narrow slit the peak response decayed approximately exponentially with displacement from the centred position. 3. With variation in the area of a centred circular patch, the peak response increased in a graded manner with stimulus area but was not proportional to area. 4. The model of electrical coupling in the horizontal cell layer proposed by Naka & Rushton (1976) was applied to the results. For the case of dim illumination a simplification is applicable, and the voltage distribution for circular and slit‐shaped patches of light can be expressed in terms of two unknowns: the voltage resulting from diffuse illumination and a characteristic 'length constant'. 5. The measured variation of response amplitude was well described by the theory. Measured length constants were distributed from less than 100 mum to greater than 1 mm, and in a given cell the values determined by the slit displacement method and the area variation method were in reasonable agreement. 6. It is concluded that with dim illumination the model provides an accurate description of the voltage spread in the cells. Deviations were found to occur at higher intensities and possible reasons are discussed. 7. The implications of the model on the measurement of resistance changes during illunination are discussed.
An estimate of the secondary spindle receptor afferent contribution to the stretch reflex in extensor muscles of the decerebrate cat.
Authors: Kanda K , Rymer W Z
Published: December 2014

1. Vibration or stretch of the medial gastrocnemius muscle in the decerebrate cat each caused a significant increase in the tension of a synergist, the lateral gastrocenmius. 2. Simultaneous vibration and stretch of the medial gastrocnemius resulted in a substantial increase of lateral gastrocnemius tension which was greater that that produced by medial gastrocnemius vibration alone. The size of this force increase was proportional to the amplitude of medial gastrocnemius stretch, for the limited range of amplitudes examined. 3. Since the discharge of the medial gastrocnemius I a afferent fibres was held constant by vibration, the additional tension in lateral gastrocnemius provoked by medial gastrocnemius stretch must have resulted from the activation of an excitatory pathway separate from the I a afferent system. The secondary spindle afferent pathway was considered to be the most likely candidate. 4. The contributions of the Ia afferents and the additional stretch induced excitation to the stretch reflex were compared. The Ia potency was calculated from the ration of tonic vibration reflex force and the vibration frequency. The total Ia contribution to the stretch reflex, which was estimated from the product of this ratio and the primary ending stretch sensitivity, seemed modest, and was consistently smaller than the proposed secondary contribution. 5. The medial gastrocnemius nerve was subjected to anodal blockade at a strength sufficient to eliminate Ia transmission. Under these conditions, the lateral gastrocnemius excitation produced by medial gastrocnemius stretch or vibration was largely eliminated. When lateral gastrocnemius vibration was superimposed, the excitatory effect of medial gastrocnemius stretch was partly restored suggesting that some central facilitation by group Ia afferents may be necessary for group II pexcitatory effects to be manifested. 6. Although the additional excitatory actions of medial gastrocnemius stretch were examined exclusively in a synergist, it is suggested that similar effects are likely to occur in the homonymous stretch reflex.
Influence of medial preoptic‐anterior hypothalamic area stimulation of the excitability of mediobasal hypothalamic neurones in the rat.
Authors: Renaud L P
Published: December 2014

1. Extracellular action potentials recorded from 798 neurones in the mediobasal hypothalamus (MBH) of pentobarbitone anaesthetized male rats were analysed for a change in excitability following stimulation in the medial preoptic and anterior hypothalamic areas. 2. An increase in excitability characteristic of orthodromic excitation was observed from 11‐5% (n=92) of MBH neurones. Latencies for excitation were shorter for cells tested with anterior hypothalamic area stimulation (n=42; mean 5‐4 +/‐ 2‐6 msec S.D.) than for cells tested with medial preoptic stimulation (n=50; mean 15‐2 +/‐ 7‐2 msec S.D.). With spontaneously active neurones, excitation was followed by a decrease in excitability lasting 150‐250 msec. An initial decrease in excitability, suggestive of post‐synaptic inhibition, over a wide latency range (4‐30 msec) and with duration of 100‐400 msec was observed from 3‐6% of MBH neurones. 3. Features of antidromic invasion were observed from 149 MBH neurones. From the medial preoptic area, the latency range was 0‐5‐38 msec (mean 7‐8 +/‐ 5‐5); from the anterior hypothalamic area the latency range was 0‐4‐9‐5 msec (mean 3‐1 +/‐ 2‐3). Occasionally an abrupt decrease in latency followed an increase in stimulus intensity. Most cells followed paired stimuli at frequencies up to 500 Hz. Axon conduction velocities were estimated to be under 2‐0 m/sec. Antidromic invasion was usually followed by a decrease in excitability lasting approximately 100‐150 msec. 4. Twenty MBH neurons displayed antidromic invasion from both the medial preoptic or anterio hypothalamic areas and one other stimulation site: the median eminence (five cells); the amygdala (six cells); the region of thalamic nucleus medialis dorsalis (three cells) and the midbrain periaqueductal gray (six cells). Interaction studies indicated that the axons of these cells branched close to the origin of the axon itself. 5. Antidromic invasion from the surface of the median eminence identified thirty‐nine tuberoinfundibular neurones. Stimulation in the medial preoptic and anterior hypothalamic area produced orthodromic excitatory (n = 5) and inhibitory (n = 4) actions on HVM neurones, but was without an action on most other neurones (n = 30). Tuberoinfundibular neurones in the ventromedial nucleus also responded to stimulation in the amygdala, but usually at latencies greater than that for medial preoptic area evoked responses. 6. These observations indicate a close relationship between MBH neurones and cells located in both the amygdala and the medial preoptic‐anterior hypothalamic area. The data for tuberoinfundibular neurones indicates that several extrahypothalamic areas may send fibres to these cells. These pathways may be important for the adaptive neuroendocrine responses reported in the literature.
Control of hepatic and intestinal blood flow: effect of isovolaemic haemodilution on blood flow and oxygen uptake in the intact liver and intestines.
Authors: Lautt W W
Published: December 2014

1. Limited isovolaemic haemodilution was produced in cats by addition of dextran 75‐Ringer solution to an extracorporeal blood reservoir connected in series with the cat. Total hepatic venous outflow was neasured using a hepatic venous long‐circuit and hepatic arterial flow was measured with an electromagnetic flow probe. Oxygen uptake was monitored in the guts and liver. Na‐pentobarbitone anaesthesia was used. 2. Following reduction of the haematocrit (from 31 to 22) the oxygen uptake of the gut segment and liver were maintained. Gut conductance increased to 125% of control while the oxygen extraction ratio increased to only 109%. The hepatic arterial conductance did not change in spite of a greatly reduced (to 68%) oxygen delivery. Hepatic extraction increased to 140% of control. 3. The hepatic artery did not dilate to maintain constant oxygen supply to the liver thus confirming our previous observation that blood flow is not coupled to hepatic metabolism. 4. Oxygen extraction in the gut correlated well with changes in portal blood flow but not with changes in vascular conductance, arterial blood pressure or oxygen delivery. 5. The blood flow of the gut (vascular beds draining into the portal vein in the splenectomized preparation) was controlled in a manner that prevented changes in portal venous PO2 in spite of a reduction in oxygen content. Local PO2 and perhaps pH, are suggested as the factors controlling gut blood flow following haemodilution. 6. Changes in portal blood flow correlated with changes in portal vascular (intrahepatic) conductance such that increased portal flow produced an increased portal conductance thereby maintaining portal venous pressure constant.
The contribution of alterations in cardiac output to changes in arterial pressure reflexly evoked from the carotid sinus in the rabbit.
Authors: Humphreys P W , Joels N
Published: December 2014

1. The reflex cardiovascular effects of changes in pressure within the vascularly isolated carotid sinus were examined in seventeen anaesthetized rabbits. The opposite sinus was denervated and both aortic nerves were divided, 2. Comparison of the mean values at sinus pressures of 40 and 200 mmHg showed a large reduction in systemic arterial pressure from 126 to 58 mmHg and a moderate reduction in heart rate, from 287 to 253 beats min‐1. Cardiac output, measured by thermal dilution, showed only a small change, a fall from 160 to 148 ml. min‐1 kg‐1. 3. By contrast with this reduction in cardiac output of just over 7%, total peripheral resistance, derived by dividing mean arterial pressure by cardiac output, was halved, falling from 0‐48 to 0‐41 mmHg ml.‐1 min kg. 4. Thus in the anaesthetized rabbit changes in cardiac output make only a small contribution to the changes in systemic pressure evoked by alterations in carotid sinus pressure. Changes in total peripheral resistance are principally responsible for the effect on systemic pressure. 5. Though the changes in output of the heart were small, there were considerable changes in the work done by the left ventricle which was approximately halved when carotid sinus pressure was raised from 40 to 200 mmHg.
Ouabain‐sensitive ion fluxes in the smooth muscle of the guinea‐pig's taenia coli.
Authors: Widdicombe J H
Published: December 2014

1. Tissues with raised intracellular Na levels, produced by incubation in K‐free media, were used throughout. The uptake of 42K by these Na‐loaded tissues was followed for 10 min in the presence and absence of 1‐37 X 10(‐4) M ouabain, this being sufficient to inhibit Na pumping maximally. Subtraction of the uptake seen in the presence from that seen in the absence of ouabain gave estimates of the pumped ouabain‐sensitive K uptake. 2. In Na‐free (MgCl2) medium this depended on the [K]0 in a sigmoidal fashion with a half maximal [K]0 for activation of some 4mM. The maximal uptake of K was 3 m‐mole/kg.min corresponding to a transmembrane flux of some 12‐5 p‐mole. cm‐2.sec‐1. 3. In the presence of Na the K activation curve became more obviously sigmoid and higher concentrations of K were needed to achieve a given active K influx. The results were well fitted by assuming that Na and K competed for two identical, non‐interacting sites on the external pump face. 4. Addition of K during the efflux of 24Na into a Na‐free (MgCl2) medium led to an increased rate of tracer loss. The magnitude of this increase depended on the [K] used in a hyperbolic fashion and it was abolished by addition of ouabain. The [K] causing half‐maximal activation of ouabain‐sensitive Na efflux was in the order of 1‐2 mM. 5. When the [K] in the uptake media was 1‐5 mM; Na, Li, Rb and Cs all inhibited ouabain‐sensitive K uptake, the order of effectiveness being Rb greater than Cs greater than Na greater than Li. With a E1TKA10 OF 0‐15 MM low concentrations of Cs and Rb were shown to stimulate K uptake. Such an effect is predicted by assuming two ion binding sites on the pump's outer face, and that the pump can translocate mixtures of K and either Rb or Cs...
Intracerebroventricular taurine in rabbits: effects of normal body temperature, endotoxin fever and hyperthermia produced by PGE1 and amphetamine.
Authors: Harris W S , Lipton J M
Published: December 2014

1. Intracerebroventricular (I.C.V.) injections of taurine into rabbits resting at an ambient temperature (Ta) of 10 degrees or 23 degrees C caused hypothermia but at 30 degrees C ambient temperature, rectal temperature was unchanged. 2. An I.C.V. bolus of 0=5 mg taurine immediately followed by a slow infusion of taurine (0‐01‐‐0‐2 mg/min) into rabbits at 23 degrees C ambient temperature caused sedation and peripheral vasodilation and blocked the febrile response to Salmonella typhosa endotoxin (1 microng/kg i.v.). Sustained fevers, characteristic of fevers caused by central administration of pyrogens, developed after taurine infusions were stopped. Control infusions of taurine at the same rates in the same rabbits when they were afebrile had little effect on rectal temperature. 3. An I.C.V. injection of 0‐5 mg taurine reduced the hyperthermia caused by prostaglandin E1 (PGE1; 2 microng) given I.C.V. A dose of 5‐0 mg not only blocked PGE1 hyperthermia but also caused marked hypothermia. 4. Bilateral injections of taurine into the preoptic/anterior hypothalamic region, at sites where injections of Salmonella typhosa endotoxin caused long‐lasting fevers, had no effect on rectal temperature. Similar injections into the reticular substance of the medulla oblongata, in the region believed to be concerned with a secondary temperature control function, were also without effect on body temperature. 5. Taurine (0‐5 and 5‐0 mg, I.C.V.) had no consistent effect on hyperthermia induced by amphetamine (2 mg/kg, I.V.) 6. We conclude that the hypothermic effect of taurine is not due to an action on the central neurone pool or pools concerned with the integrative control of thermoregulatory effectors. This amino acid appears to inhibit neuronal activity in efferent pathways which control peripheral vasomotor tone and heat production and to depress the level of arousal. Taurine delays the onset and extends the duration of endotoxin‐induced fever, perhaps by two separate action: by inhibiting activity in central thermoregulatory pathways and by promoting accumulation of endogenous pyrogen in the brain.
Very small, very short‐latency changes in human breathing induced by step changes of alveolar gas composition.
Authors: Cunningham D J , Drysdale D B , Gardner W N , Jensen J I , Petersen E S , Whipp B J
Published: December 2014

1. Three healthy young males were maintained for sessions of about 1 hr in a state of mild asphyxia (PA,O2 approximately 55, PA,CO2 approximately 45 torr), i.e. with moderately strong drives from both arterial and intracranial chemoreceptors. Tidal volume (VT), breath duration (TT) and duration of inspiration (TI) were recorded, and ventilation (VE) and duration of expiration (TE) were derived breath by breath. 2. The arterial chemoreceptor component of the drive was briefly and abruptly reduced, perhaps silenced, by three separate procedures: the inspiratory pathway was connected for two breaths to a second gas supply line containing, B, hypoxia with Pi,CO2 zero (removal of hypercapnia with maintained hypoxia); C, pure oxygen (removal of asphyxia); and D, oxygen with 40 torr added PCO2 (removal of hypoxia with maintained hypercapnia). In controls, A, the second inspiratory line contained the maintenance mixture so that the switch involved no change of inspiratory gas composition. Each type of test was repeated twenty‐four times on each subject. 3. Responses attributable to silencing of arterial chemoreceptors (i.e. with 1 1/2‐‐3 breath latencies about equal to the lung‐to‐ear circulation time) are reported elsewhere. 4. Very small responses, occurring only half a respiratory cycle after first inhalation of the test mixture, were detected by pooling all responses of each kind from all subjects. When hypoxia was withdrawn, with (C) or without (D) simultaneous withdrawal of hypercapnia, VT and VE were reduced by 3 and 2% respectively, probably because gas mixtures containing high oxygen concentrations are appreciably more viscous than hypoxic mixtures and so require more effort to breathe in and out. When hypercapnia was withdrawn with (C) or without (B) simultaneous withdrawal of hypoxia, TE was significantly lengthened (mean, + 65 +/‐ 18 msec), 5. The change of TE was discussed in relation to known effects of CO2 on airway receptors in the dog.
Nervous outflow from skeletal muscle following chemical noxious stimulation
Authors: Mense S.
Published: December 2014

1. In order to determine the nervous outflow from skeletal muscle during chemically induced muscle pain, the impulse activity of various types of muscle afferents in response to close intra‐arterial injections of pain‐producing substances (bradykinin, 5‐hydroxytryptamine, histamine and potassium) was studied in anaesthetized cats using a single fibre recording technique.

2. By administration of algesic agents in doses which produce pain in man and pain reactions in animals, about half of the group IV and two thirds of the group III muscle afferents could be activated. In contrast, group II and group I afferent units were usually not excited by chemical noxious stimulation. If effects at all occurred in the thick myelinated afferents, they consisted of a depression of the fibre activity rather than of an activation.

3. The qualitative features of the discharges of group III muscle afferents induced by chemical stimulation resembled those of the group IV units very closely. The group III units differed from the group IV afferents in that their responses to a given dose of bradykinin were of greater magnitude.

4. It is concluded that the chemically induced muscle pain is probably mediated by certain portions of the group IV and group III afferents, whereas the reactions of group II and group I units to algesic agents are such that a contribution to muscular chemo‐nociception seems improbable.
Calcium currents and conductances in the muscle membrane of the crayfish
Authors: Henček M. , Zachar J.
Published: December 2014

1. Membrane currents in calcium type muscle membrane of the cray‐fish Astacus fluviatilis were analysed by a method in which a membrane microarea was isolated by circulating sucrose rings contacting the fibre perpendicular to the fibre surface.

2. The early calcium inward currents were separated from the total membrane currents by subtraction of the early and delayed potassium currents from the total membrane current.

3. The isolated calcium currents show a time course characteristic for a transient change of calcium conductance. The presence of inactivation was further checked by the time course of the tail currents at the end of voltage clamp pulses of variable duration.

4. The reversal potential of the early calcium currents determined from the current—voltage relations was +85 ± 4·2 mV. The calcium potentials were used to express the calcium currents in the form of chord conductances.

5. Calcium conductances (gCa) as functions of time and voltage were found to be described quantitatively on the assumption that gCa is determined by two variables (m and h), according to the equation gCa = m6hḡCa, where ḡCa is a constant and m and h obey first order differential equations of the Hodgkin—Huxley type.

6. The activation parameters of the gCa were determined by fitting the solutions of the above equations to the experimental values of the gCa. This method was also used to check the inactivation parameters.

7. The inactivation parameters of the gCa were obtained from the inactivation curves, which were determined for several membrane potentials by variation of the duration of the conditioning step.

8. The average calcium conductance constants were tabulated and compared with sodium conductance constants in excitable membranes.
The force‐velocity relationship in vertebrate muscle fibres at varied tonicity of the extracellular medium
Authors: Edman K. A. P. , Hwang J. C.
Published: December 2014

1. The relationship between active force and velocity of shortening was studied during tetanic contraction of isolated semitendinosus muscle fibres of the frog (0·5‐2·0° C). Measurements were carried out with the fibre immersed in isotonic (1·00R) Ringer solution and in solutions that were made hypotonic by reduction of NaCl (osmolality 0·62 and 0·81 of normal Ringer) and hypertonic by addition of sucrose (osmolality 1·22 and 1·44 of normal Ringer).

2. The force—velocity relation was hyperbolic at loads lower than 80% of measured isometric force (P0) but exhibited a reversed curvature between 0·8P0 and P0. The maximum velocity of shortening was determined in two different ways: (i) by extrapolation to zero load from force—velocity data truncated at 0·8P0 (computer fitting of hyperbola, leastsquares method) and (ii) by recording the time required to take up the slack of the fibre after a quick release during tetanus.

3. Isometric force and maximum speed of shortening both changed inversely with the tonicity of the extracellular medium. Immersion of the fibre in 0·81R hypotonic solution caused active tension and shortening velocity to increase by 10 ± 1% (mean ±
S.E. of mean, n = 14) and 12 ± 1%, respectively. Conversely, force and shortening velocity decreased by 12 ± 1% (n = 13) and 22 ± 2% when normal Ringer was replaced by 1·22R hypertonic solution. These changes doubled when the tonicity was altered from normal Ringer to 0·62R and 1·44R, respectively.

4. Changes in fibre cross‐sectional area equivalent to those obtained in the 0·81R and 1·22R solutions (+11% and ‐13%, respectively) were produced by varying the sarcomere length within the range 2·0‐2·5 μm in the normal Ringer solution. Maximum velocity of shortening remained very nearly constant under these conditions, indicating that the shortening velocity, like the isometric force, is not critically dependent on changes in myofilament lattice width over the range considered.

5. The results support the view that both shortening velocity and active force are modulated by changes of the intracellular ionic strength above and below the level that normally exists in the intact muscle fibre.
Evidence for antral inhibition of pentagastrin from experiments using mucosal cooling.
Authors: Kondo T , Magee D F
Published: December 2014

1. The acid secretion of the fundic mucosa in Heidenhain pouches in response to pentagastrin became progressively less as the pouch mucosa was cooled. 2. When a cooled Heidenhain pouch in an animal receiving pentagastrin was warmed, acid and pepsin secretion from the main stomach was depressed. Change from warm to cool produced no obvious effect. 3. In animals receiving pentagastrin continuously, but not in those receiving histamine, lowering the temperature in an antral pouch, or the application of local anaesthetics to its mucosa, increased acid and pepsin secretion from the main stomach when the antral pouch was fully innervated. 4. This effect could readily be abolished by ganglionic and beta‐adrenergic blockade, but not by bilateral vagal block in the neck, thus suggesting a sympathetically mediated inhibitory mechanism of pyloric origin. 5. The effect of indirect vagal stimulation, using 2‐deoxy‐D‐glucose on secretion from the main stomach, was augmented by pyloric antral local anaesthesia and depressed by antral cooling.
Action of oleic acid on the exocrine pancreatic secretion of the conscious rat: evidence for an anticholecystokinin‐pancreozymin factor
Authors: Laugier R. , Sarles H.
Published: December 2014

The effects on exocrine pancreatic secretion of an intraduodenal infusion of oleic acid (2 ml in 60 min) has been assessed in conscious rats provided with a new type of duodenal cannula permitting the normal flow of pancreatic juice, but not of bile, between experiments.

1. Intraduodenal oleic acid infusion induces an increased secretion of water and bicarbonate which is still significantly above basal values 90 min after the end of infusion. Protein output increased during the infusion, but protein concentration and output significantly decreased under basal levels 120 min and 150 min after infusion (respectively ‐63 and ‐57% of basal values at 150 min).

2. No inhibition was found when oleic acid was introduced into the caecum or into the first 20 cm of ileum isolated from the rest of small intestine. On the contrary, inhibition of protein secretion was induced immediately by intra‐ileal oleic acid infusion.

3. Inhibition of protein secretion secondary to intra‐ileal oleic acid infusion was transmitted from a donor rat to a receiver rat by means of a cross‐circulation.

4. It is concluded that oleic acid induces an immediate and long lasting increase in water and bicarbonate secretion. During the infusion of oleic acid, protein output is increased, followed by an inhibition. This delayed inhibition stems from the second part of the small intestine and was transferred from one rat to another by cross‐circulation: it is speculated that oleic acid releases in the conscious rat (from the distal part of the small intestine) a hormonal factor inhibiting pancreatic secretion.
The relation between tidal volume and inspiratory and expiratory times during steady‐state carbon dioxide inhalation in man
Authors: Gardner W. N.
Published: December 2014

1. Ambiguities and discrepancies in the published descriptions of the patterns of breathing in man have been re‐investigated.

Steady‐state hyperpnoea during rest was induced in normal subjects of both sexes by means of CO2 inhalation, usually in high O2, but sometimes in low (PA, O2 ∼ 200 and 55 torr respectively).

2. The relations between mean tidal volume V̄T and mean times for inspiration T̄I and expiration T̄E were satisfactorily divided into lower and upper parts (ranges 1 and 2) in nineteen out of thirty‐three experiments using an objective least‐squares method, and polynomials were fitted separately to each of the following pairs of variables V̄T,lower, T̄I; V̄T,lower, T̄E; V̄T,upper, T̄I; V̄T,upper, T̄E.

3. The breakpoints occurred when V̄T was about one third of vital capacity, but there was much variation between subjects.

4. In range 2, V̄T was inversely related to both T̄I and T̄E and there appeared to be linkage between T̄I and T̄E, all as described by Clark & Euler (1972). The relation suggested by Hey, Lloyd, Cunningham, Jukes & Bolton (1966) over range 2 was not confirmed.

5. The main part of the relation described by Hey et al. (1966) is concerned with range 1. Here the relation between V̄T and T̄I was variable; slight, but significant negative correlation predominated. V̄T was, on the other hand, strongly and inversely related to T̄E, and plots of (T̄E — T̄I) against V̄T over both ranges showed even less scatter. Hence (a) T̄E is probably related to V̄T through two mechanisms, one involving a link with TI and another prominent one being quite independent of TI, (b) most changes of respiratory frequency in normal man are brought about by change of TE rather than of TI, and (c) there is no region of constant frequency as implied by Clark & Euler (1972).
Respiratory modulation of baroreceptor and chemoreceptor reflexes affecting heart rate through the sympathetic nervous system
Authors: Davis Anne L. , McCloskey D. I. , Potter Erica K.
Published: December 2014

1. Brief stimuli were delivered to the carotid body chemoreceptors or the carotid sinus baroreceptors at different phases of the respiratory cycle in anaesthetized dogs. Chemoreceptor stimulation was achieved by injecting small volumes (0·2‐0·5 ml.) of warmed saline equilibrated with CO2 near to the carotid bodies on both sides. Baroreceptor stimulation was achieved by injecting larger volumes (2‐5 ml.) of saline equilibrated with air into the region of the carotid bifurcation on both sides, after first clamping the common carotid arteries.

2. When the vagus nerves were intact, but sympathetic nervous effects on heart rate were blocked by administration of propranolol, there was a prompt and pronounced bradycardia evoked when either baroreceptor or chemoreceptor stimuli were given in expiration, but little or no change in heart rate when they were given in inspiration.

3. When the vagus nerves were cut, but sympathetic nervous function was intact, respiratory modulation of both baroreceptor and chemoreceptor reflex effects on heart rate could still be demonstrated. The bradycardia evoked by either stimulus was more marked for stimuli given in expiration than for stimuli given in inspiration. A complementary response pattern for brief decreases in baroreceptor stimulation (carotid occlusions) was demonstrated: the tachycardia evoked by occlusions timed during inspiration was greater than that evoked by occlusions timed during expiration. All the reflex effects were mediated by the sympathetic system because they were abolished by administration of propranolol.

4. Typically, the sympathetic reflex effects were slight in comparison with the vagal reflexes evoked by either chemoreceptor or baroreceptor stimuli.
Neuromuscular transmission in arterioles of guinea‐pig submucosa.
Authors: Hirst G D
Published: December 2014

1. Intracellular recordings were made from arterioles lying in the submucosa of guinea‐pig small intestine. 2. Low frequency perivascular nerve stimulation evoked subthreshold excitatory junction potentials which facilitated. 3. Higher frequency stimulation caused summation of excitatory junction potentials and the initiation of muscle action potentials. 4. Arteriolar constriction was only observed following the initiation of a muscle action potential.
Increased urinary kallikrein excretion during prostaglandin E1 infusion in anaesthetized dogs and its relation to natriuresis and diuresis.
Authors: Mills I H , Obika L F
Published: December 2014

. The effect of intra‐arterial prostaglandin E1 (PGE1) infusion on urinary kallikrein, sodium, potassium and water excretion was studied in normal anaesthetized dogs. 2. Infusion of PGE1 caused a dose‐related increase in urinary excretion of kallikrein, sodium, potassium and water as well as an increase in renal blood flow (R.B.F.) and a fall in urinary osmolality and renal vascular resistance. 3. The changes occurred in the absence of appreciable changes in inulin clearance (Cin), arterial blood pressure, haematocrit, and plasma sodium and potassium concentrations. 4. The increased urinary kallikrein excretion correlated positively with the natriuresis, diuresis and kaliuresis and the increase in renal blood flow, but negatively with the urinary osmolality and renal vascular resistance. 5. It is concluded that renal kallikrein is involved in the renal response to arterial infusion of PGE1.
Site of intestinal dipeptide hydrolysis.
Authors: Wiseman G
Published: December 2014

1. Sacs of everted small intestine of the hamster have been used to study the site of final hydrolysis of twelve dipeptides. 2. The results suggest that L‐alanyl‐glycine, glycyl‐glycine, L‐valyl‐L‐valine, L‐alanyl‐L‐valine, L‐valyl‐L‐alanine and L‐prolyl‐glycine are hydrolysed beyond the locus of the active transport mechanism for D‐glucose, perhaps even within the cell. These may be designated class 1 (deep) dipeptides. 3. In contrast, superficial (perhaps even surface) hydrolysis seems to occur with L‐alanyl‐L‐alanine, L‐leucly‐L‐leucine, glycyl‐L‐alanine, L‐alanyl‐L‐leucine, L‐leucyl‐L‐alanine and glycyl‐L‐proline. These may be designated class 2 (superficial) dipeptides. 4. All the dipeptides were able to partially inhibit D‐glucose active transport, the findings supporting the view that more than one mechanism may exist for the active absorption of the sugar.