Quarterly journal of experimental physiology (Cambridge, England)最新文献

The effects of cold exposure on arterial and mammary venous concentrations of thyroxine and oestrone sulphate, and on mammary blood flow, were measured in goats during different stages of pregnancy and lactation. There were no significant differences in net mammary uptake of thyroxine in four non-pregnant lactating goats exposed for 30 h to cold (-3 +/- 2 degrees C) or control (20 +/- 2 degrees C) temperatures. Cold exposure for 30 h of six lactating goats (approximately 85 d pregnant) stimulated a net mammary release into the circulation of oestrone sulphate (mean 294 ng/min); plasma cortisol concentrations also increased. Cold exposure at approximately 30 d of pregnancy increased cortisol concentrations but had no effect on release of oestrone sulphate.

The effects of fetal pancreatectomy on the uptake of oxygen, glucose and lactate by the fetus, uterus and uteroplacental tissues were investigated in chronically catheterized sheep during the last third of gestation. Pancreatectomy reduced the uptake of glucose by the fetus but had little apparent effect on glucose uptake by the uterus or uteroplacental tissues. The mean umbilical uptake of glucose by the pancreatectomized fetuses was 10.4 +/- 1.1 mumol/kg . min (n = 4) which was significantly less than the value observed in the intact fetuses (24.5 +/- 2.7 mumol/kg . min, n = 4, P less than 0.01). When all the data from the pancreatectomized and intact fetuses were combined, there was a significant positive correlation between the plasma insulin concentration in utero and the umbilical uptake of glucose (r = 0.95, n = 14, P less than 0.01). The glucose/oxygen quotient in the pancreatectomized fetuses (0.32 +/- 0.02, n = 9) was significantly less than the value observed in the intact fetuses (0.59 +/- 0.04, n = 6, P less than 0.01). There was also a significant positive correlation between the glucose/oxygen quotient and the plasma concentration of insulin in the fetus (r = 0.73, n = 59, P less than 0.01). Pancreatectomy had no significant effect on the fetal lactate/oxygen quotient or on the uptake of oxygen or lactate by any of the tissues. These observations demonstrate that the endogenous concentration of insulin is a physiological regulator of glucose uptake by the fetal tissues.

An objective method for assessing customary physical activity has been described, based on heart rate and footfall signals recorded on magnetic tape using small body-borne recorders. Computer analyses were used to obtain indices of the intensity and duration of periods of physical activity using both biosignals. Threshold values were set for each individual at a heart rate related to a standard walking speed of 4.8 km . h-1 (3 miles per hour). Four activity indices were defined in terms of time spent above this threshold and the intensity of the heart rate elevation above it, applying criteria relating to the duration of periods of activity or the concurrent activation of the walking signal. The choice and validity of these indices are discussed, and results for several groups of subjects presented. Three groups of subjects aged over 60 years were studied before and after retirement: twenty-five were steel-workers and thirty-nine were factory-workers (men and women). Rather low levels of activity were recorded. After one year of retirement the female factory workers showed a significant decrease in activity. In men this was found only after several years of retirement had elapsed.

[3H]noradrenaline ([3H]NA) release from the isolated main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal (corticosterone, 5 X 10(-5) M) uptake blockers. 10(-4) M ouabain significantly increased the [3H]NA release in normal external ionic environments after an initial delay (20-30 min). Excess K (23.6 mM) failed to affect the resting [3H]NA outflow, significantly inhibited the ouabain-stimulated [3H]NA release and shortened the initial delay by about 10-20 min. Higher concentration of K (47 X 2 mM) enhanced the outflow of [3H]NA. In the absence of external Ca and in the presence of 1 mM EGTA, 23.6 mM-K failed to exert an inhibitory action on ouabain evoked transmitter release. Higher concentrations of K, however, significantly inhibited the [3H]NA-releasing effect of ouabain without changing the resting outflow of labelled neurotransmitter. The initial delay of ouabain-evoked [3H]NA release was shortened by increasing the concentration of K. Total substitution of external Na by K (143.3 mM) increased the [3H]NA release in the absence of external Ca. After the Na gradient was re-established in Ca-free solution the release of [3H]NA was terminated. Under these conditions the NA-releasing action of ouabain was dependent on the preceding perfusing period in Na-free solution, being smaller if longer exposure time was used. When external Na was substituted by Li (137.4 mM) in Ca-free solution the [3H]NA release was dramatically increased. After Na readmission ouabain was ineffective in producing transmitter release. It is suggested that in the main pulmonary artery of the rabbit, when the electrochemical gradient of Ca is reversed, ouabain is effective in producing transmitter release if the internally stored Ca has not been completely lost. Since in Ca-free solution the ouabain-evoked [3H]NA release can be inhibited by external K it seems that the transmitter release observed is due to a Na-dependent release of intracellular Ca rather than the penetration of ouabain into the cell followed by direct inhibition of the active transport of internal store membranes.

Stimulation of autonomic nerves supplying smooth muscle tissues often evokes either an e.j.p. or an i.j.p. which involves a shift in the membrane potential such that the entry of calcium into the cell through voltage-sensitive calcium channels is likely to be increased or decreased respectively. In smooth muscle which freely discharges action potentials either spontaneously or in response to excitatory influences in vivo, the change in membrane potential will alter the rate of action potential discharge and so the tension developed by the smooth muscle. In this way there is modulation of the rate of entry of calcium, or its release within the cell, by a voltage-dependent mechanism entrained by the junction potential, as the action potential represents the operation of voltage-dependent calcium channels. In smooth muscles not freely discharging action potentials, the numbers of open calcium channels may change with depolarization, or even hyperpolarization, so the junction potential again brings into play a voltage-dependent mechanism of calcium entry. However, a dual mechanism of neurotransmission seems to operate at many autonomic nerve-smooth muscle junctions such that voltage-independent mechanisms coexist with voltage-dependent mechanisms. It is now generally accepted that activation of receptors on smooth muscle cells caused by bathing smooth muscles in solutions containing excitatory transmitters can bring into operation processes which are not voltage-dependent and which do not depend on modulation of the rate of action potential discharge. Up to the present it has been by no means certain that when released from autonomic nerves these excitatory transmitters (ACh, noradrenaline, substance P and n.a.n.c. excitatory transmitters) could also act in the same voltage-independent way - not least because studies of smooth muscle cells at the cellular level have been dominated by membrane potential recording (by micro-electrode) which has revealed the e.j.p. or some form of depolarization as a seemingly ubiquitous feature of excitatory autonomic junctions of nerve and smooth muscle cells. However, experiments show that under conditions when the e.j.p. and/or the action potential are abolished or severely impaired by drug application, substantial nerve-evoked smooth muscle contractions may occur at many autonomic junctions. Conversely, severe impairment of nerve-evoked contraction may occur in some cases with excitatory-receptor antagonists without loss, or even in some cases any impairment, of the e.j.p. which presumably depends on a different receptor type.(ABSTRACT TRUNCATED AT 400 WORDS)

Morphological changes in peripheral nerve caused by the venoms of the scorpions Leiurus quinquestriatus and Centruroides sculpturatus were compared with those caused by Phoneutria nigriventer spider venom. Both scorpion venoms are known to delay the inactivation of sodium currents, Centruroides venom also altering the voltage dependence of sodium gating. Venom was injected by means of a glass micropipette into the sciatic nerves of anaesthetized mice. After survival times ranging from 15 min to 24 h the nerves were examined by light and electron microscopy. The two scorpion venoms caused alterations virtually identical to those produced by Phoneutria venom, which included swelling of the nodal axoplasm and accumulation of fluid in the periaxonal space of myelinated fibres. These alterations were most marked after 1 to 2 h and had largely disappeared by 24 h. Pre-treatment of the nerves with tetrodotoxin, which specifically blocks sodium channels, completely prevented both the nodal axoplasmic swelling and the periaxonal oedema. It seems likely that these effects result from an action common to the three venoms and that this is probably a delay in the inactivation of sodium current at the node of Ranvier.

The retrograde transport of horseradish peroxidase from a white ramus communicans has been used to define the precise segmental location of sympathetic preganglionic cell bodies in the spinal cord of the cat and dog. All labelled cells were found ipsilaterally and were confined to the spinal cord segment from which the ramus originated. Most lay in the intermediolateral cell column and the immediately adjacent white matter, though others were scattered in more medial areas of the grey matter. We suggest that the observed distribution of sympathetic preganglionic neurones, the orientation of their processes and the paths taken by their axons are a direct result of cell migration during the embryological development of the spinal cord.

Adaptive changes occur in nutrient uptake following intestinal resection. A previously validated in vitro technique was used to measure the rate of uptake of solutes six weeks following surgical removal of the distal half of the small intestine in the rabbit. The rate of jejunal uptake of a homologous series of fatty alcohols, cholesterol, and six bile acids was unchanged in the resected animals. The uptake of short- and long-chain length fatty acids was also unchanged following resection, although there was a modest but significant increase in the uptake of decanoic and dodecanoic acid. The incremental change in free energy, integral of delta Fw----l, was increased in the jejunum of resected animals when assessed with the medium chain-length fatty acids, but was unchanged when estimated from the uptake of long chain-length fatty acids. The value of delta integral of Fw----l for bile acids was similar in the jejunum of control and resected animals. There was an increase in the maximal transport rate (Jdm) for D-glucose, galactose and L-leucine, an increase in the Michaelis constant (Km) for 3-O-methylglucose, and an increase in both the Jdm and Km for fructose. There was no change in the passive component of the uptake of these solutes following intestinal resection. In the resected animals there was no significant increase in the height, width, and surface area of the jejunal villi, the number of mucosal cells per villus, or in the mucosal surface area, although there was a significant increase in the weight of the scraped mucosa and in the height of the microvilli. The modifications in the active and passive kinetic constants were not related to the alterations in the microvillus surface area, and changes in the Km or delta integral of Fw----l were not due to any variation between control and resected animals in the effective resistance of the intestinal unstirred water layer. These results indicate that, ileal resection was not associated with changes in the effective resistance of the intestinal unstirred water layer; the variable changes in the uptake of passively adsorbed solutes following resection suggests a functional heterogeneity of the villus towards passive permeation; estimation of the incremental change in free energy of the intestine using a homologous series of saturated fatty acids may provide variable results depending upon the chain length of the probes.(ABSTRACT TRUNCATED AT 400 WORDS)