摘要:

To elucidate why arterial pH and carbon dioxide (Paco2) modify the pancreatic H+/ HCO‐3secretory response to secretin stimulation, experiments were performed on anaesthetized pigs, recording the effects of arterial pH andPaco2on exocrine H+/ HCO‐3secretion and on morphology of pancreatic duct cells. Duct cells contained numerous cytoplasmic vesicles at secretory rest. Their number more than doubled during elevation of Paco2from 5.5 to 11.0 kPa. At arterial pH 7.40, maximal secretin stimulation cleared the cytoplasm of duct cells of more than 90% of the vesicles. At highPaco2, this was accompanied by doubling the basolateral plasma membrane area and a 30% higher secretion rate than atPaco25.5 kPa. Lowering arterial pH to 7.0 more than halved the secretin‐induced vesicle clearance of duct‐cell cytoplasm as well as exocrine H+/HCO‐3secretion and abolished the secretin‐dependent basolateral membrane area changes. Supramaximal secretin stimulation did not reverse the inhibitory effect of severe metabolic acidosis on secretion. It is concluded that Paco2and arterial pH may modify the secretory response to secretin through determining the incorporation of cytoplasmic vesicle material into the basolateral plasma membrane of

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08374.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The mechanisms for glucose regulation of the sodium content of the pancreatic β‐cells were examined using aggregates of cells prepared fromob/ob‐miceof a local colony. Exposure to glucose rapidly resulted in a protracted lowering of the sodium content as estimated with integrating flame photometry. Sodium became decreased after addition of 1 mmol 1‐1glucose, and this effect was maximal with 5 mmol I‐1of the sugar. The effects of low glucose concentrations on the sodium content could not be mimicked by the poorly metabolized 3‐o‐methyl‐D‐glucose, and it disappeared in the presence of the metabolic inhibitor antimycin A. The significance of the Na/K pump for maintaining low sodium was illustrated by a substantial increase of the element in the presence of ouabain. However, there was no indication that glucose‐induced lowering of sodium reflected activation of this pump when measuring the ouabain‐sensitive uptake of86Rb+. Neither bumetanide nor the bromo derivatives of cyclic AMP or cyclic GMP modified the glucose action on the sodium content. In evaluating whether the effect of glucose was mimicked by other inhibitors of the K+permeability it was observed that 100 μmol l‐1quinine, but not tolbutamide, decreased sodium. It is concluded that the β‐ceIl is exceptional among excitable cells in responding to its natural physiological stimulant (glucose) by reduction of sodium. Acting in this way glucose facilitates the removal

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08375.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Pregnancy increases the risk of gallstones. The physiological changes responsible for this are not clearly demonstrated. Adjustments in the enterohepatic circulation of bile acids have earlier been studied in pregnancy by methods involving dilution of labelled bile acids. In the present study the bile‐acid circulation was measured with direct drainage methods in pregnant animals and controls. It was found that the total bile‐acid‐pool size was reduced to 65% in the pregnant cat (P<0.01) and there was a reduced accumulation of bile acids in the gallbladder after fasting 24 h (P<0.01). Bile‐acid synthesis by the liver was not reduced and the relation between water and bile‐acid secretion by the liver was unchanged. It is concluded that, in the pregnant cat, the bile‐acid‐pool size is reduced due to a decreased accumulation of bile acids in the gallbladder and an increased interdigestive recycling rate of the bile‐acid pool (P<0.05). One possible explanation for the reduced accumulation of bile acids in the gallbladder is delayed emptying of the stomach, inducing a late refilling of the gallbladd

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08376.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The present study addressed the hypothesis that cardiac production of adenosine (ADO) and/or prostacyclin (PGI2) during hypoxia is augmented to a level sufficient to affect nerve‐stimulation‐induced release of noradrenaline (NA). Innervated rabbit hearts were perfused at high (95% O2) or low (8% O2) oxygen pressure. The effluxes of NA and purines from the heart were determined by HPLC and that of the PGI2metabolite by radioimmunoassay. Five minutes of hypoxia elevated effluent purines (sum of ADO, inosine, and hypoxanthine) from 1.1 μM to 6.2 μM, but did not affect the outflow of NA. The ADO receptor antagonists THEO (100–200 μM) and 8PSØT (100 μM) given during hypoxia increased the evoked outflow of NA by 77% (P<0.01) and 37% (P<0.05), respectively. Indomethacin (30 μM, a prostaglandin synthesis inhibitor) reduced the efflux of PGI2metabolite by 93 % but did notper seaffect NA outflow during simultaneous administration of THEO, either under normoxia or hypoxia. It is concluded that ADO, but not PGI2, plays a role in reducing transmitter release during hypoxia. In addition, hypoxia leads to an enhancement of transmitter release, probably unrelated to ADO or purines. The lack of effect of hypoxia alone on evoked outflow of transmitter seems to be the result of a combination of these tw

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08377.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Studies were made of the effects of continuous intravenous infusion of a synthetic atrial natriuretic factor (ANF) or, pre‐treatment with the dopamine receptor antagonist haloperidol, on the renal response in anaesthetized rats subjected to volume expansion with an isotonic solution at 2% kg‐1body weight (wt) h‐1. A time‐control group receiving vehicle alone was studied in parallel. Measurements were compared 75 and 145 min after initiation of the volume expansion. Seventy minutes of Atriopeptin II infusion at 10 μg h‐1kg‐1body wt did not significantly alter the glomerular filtration rate [control value 1.29 ± 0.10 ml min‐1g‐1kidney wt (n ‐7, mean ± 1 SEM), experimental value 1.20 ± 0.12], but increased sodium excretion by 49% (from 2.87 ± 0.56 to 4.27 ± 0.45 μmol min‐1). The arterial blood pressure was reduced by 9%. In previous investigations we found that in the same dosage Atriopeptin II increased sodium excretion 10‐fold in euvolaemic animals. In the time‐control group (n= 7) the response was similar to that in the atrial natriuretic factor‐treated animals with the exception that the blood pressure was unaltered. Thus, glomerular filtration rate showed no statistically significant change (1.28 ± 0.06vs.1.27 ± 0.09 ml min‐1g‐1kidney wt) while the sodium excretion increased by 96% (from 2.29 ± 0.22 to 4.50 ± 0.49 μmol min‐1). In animals pretreated with haloperidol (n= 5), the natriuretic response to the volume expansion was attenuated and was about ten times below that in the time‐control group. However, sodium excretion increased from 0.25 ± 0.14 to 0.69 ± 0.34 μmol min‐1and glomerular filtration rate from 1.06 ± 0.08 to 1.64 ± 0.10 ml min‐1g‐1kidney wt. Blood pressure remained unaltered. In conclusion, the natriuretic effect of Atriopeptin II is reduced in rats subjected to volume expansion while the hypotensive effect persists. This relative natriuretic hyporesponsiveness is, presumably, partly due to the previously documented increase in release of endogenous atrial natriuretic factor caused by the volume expansion, leading to receptor occupation. Haloperidol attenuates the natriuretic response to volume expansion. In the light of our previous finding that haloperidol can block the natriuretic effect of synthetic atrial natriuretic factor, we conclude that ANF is of importanc

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08378.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

A number of reports have indicated that mature blood granulocytes produce regulators that inhibit proliferation of progenitor cells in the bone marrow. However, this concept of negative feedback of granulopoiesis is still controversial. To examine whether conflicting results may depend upon the experimental set‐up, we have compared colony formation by human bone marrow cells in different growth media. Unmodified McCoy's medium, which in feeder layer cultures supports the formation of large numbers of colonies, was a poor growth medium in cultures supplied with crude or recombinant colony stimulating factor (CSF). The colony formation improved when the medium was supplemented with defined additives. In CMRL 1066 cultures, granulocyte extract (GRE) consistently caused a strong inhibition of colony formation. In contrast, with unmodified McCoy's medium, granulocyte extract enhanced colony formation in a dose‐dependent manner. The enhancing effect of granulocyte extract coincided with low colony numbers in the control cultures. The stimulatory effect of granulocyte extract in McCoy's medium, switched to strong inhibition when thymidine, a component of CMRL 1066 medium, was added. The inhibitory and stimulatory activities were found in the same molecular weight fractions (30–60 kD) after gel filtration. Both modulators in granylocyte extract appeared to be independent of monocytes and T lymphocytes in the bone marrow, as shown by removal of these cells with magnetic microspheres coated with specific monoclonal antibodies. The present work shows that regulation of cell prolifierationin vitrodepends strongly on culture conditions, such as choice of medium. It appears that thymidine acts as co‐factor for the inhibitor in granulocyte

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08379.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Department of Physiology and Biophysics, University of Lund, SwedenStructural and mechanical alterations during hypertrophy of the rat portal vein were investigated. Growth of the vessel was induced by a partial ligature of the vessel causing an increased transmural pressure. Vessel segments from animals kept with ligature for 1, 3, 5 and 7 days, were compared with vessels from sham‐operated animals. Maximal active force and vessel cross‐sectional area increased with time in the ligated group. On day 7, force and cross‐sectional area at the optimal length, were markedly increased in the ligated group (21.1 ± 1.0 mN, 0.55 ± 0.04 mm2,n= 9) compared with the control vessels (11.7 ± 1.0 mN, 0.30 ± 0.02 mm2,n= 7). Light and electron microscopy of preparations fixed at optimal length showed that the amount of smooth muscle and the cross‐sectional area of cell profiles were almost doubled in the ligated group on day 7, consistent with hypertrophy of the smooth muscle. The force per smooth muscle cell area was similar in the two groups (ligated: 132 ± 15; control: 145 ± 16 mN mm‐2,n= 4–5). The maximal shortening velocity was significantly lower in the hypertrophied group (ligated: 0.28 ± 0.02;control: 0.41 ± 0.01 optimal length s‐1,n= 6). In chemically skinned preparations, activated by maximal thiophosphorylation of the myosin light chains, force was higher in the ligated group compared to the controls but no difference in maximal shortening velocity was observed. In conclusion, the increased transmural pressure is associated with a rapid increase in the amount of smooth muscle in the portal vein. The mechanical data show that after 7 days the force generating ability of the contractile system has increased in proportion to the smooth muscle cell mass. The unaltered maximal shortening velocity in the skinned hypertrophied preparations suggests that the kinetic properties of the maximally activated contractile system are unaltered. The decreased maximal shortening velocity in the intact hypertrophied preparations may reflect alterations in the excitation

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08380.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The transport of radiolabelled albumin from tissue to blood was measured with an external detection technique in isolated, maximally vasodilated rat skeletal muscles. Initially, rat hindlimbs were perfused with albumin‐serum solutions containing [99mTc]albumin for at least 2 h, during which time the tracer accumulated interstitially. The accumulated tracer albumin was then washed out over a period of 1 h, using a tracer‐free, otherwise identical, perfusate. The wash‐out curve was multi‐exponential and the last 30‐min period was used to calculate the turnover rate constant (k), which was 7.5 times 10‐4min1(± 0.7 times 10‐4,n= 5). Moreover, if albumin was assumed to be distributed homogeneously within the interstitium, with a distribution volume (V1of 10 ml 100 g‐1, a tissue‐to‐blood clearance of albumin (ClT‐B) of 0.0075 ml min‐1100 g‐1could be calculated. By this approachClT‐Bis probably slightly overestimated, but is still only 30 % of the clearance from blood to tissue (ClB‐T), as determined in several previous studies under similar conditions. Thus, transcapillary passage of albumin is highly asymmetrical, being at least three times greater from blood to tissue than in the opposite direction. This is in agreement with the concept of the capillary walls being composed of two populations of functional pores, where macromolecules are transported from blood to tissue mainly by convection through large pores

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08381.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The influence of temperature and alternations of the stimulation scheme on fatigue development and recovery has been studied in single toe muscle fibres ofXenopus.Fatigue was in all cases produced by intermittent tetanic stimulation. In the temperature experiments easily fatigued (type 1) and fatigue‐resistant (type 2) fibres were fatigued in successive series at 10.0, 15.0 and 22.5 ±C. Lowering the temperature did not markedly influence the time‐course of fatigue development in either of the fibre types. At 22.5 ±C these fibres usually display post‐contractile depression (PCD), a delayed force suppression, during the recovery period. At the lower temperatures PCD was not observed in type 1 fibres and it was delayed in type 2 fibres. Only type 1 fibres were studied in the altered stimulation scheme experiments. Neither the time‐course of fatigue development nor the recovery process was markedly influenced by an alteration of tetanic stimulus frequency in the range of 40–80 Hz. Increasing the time‐tension area produced before the standard fatigue level (40 % of the original force) was reached, by increasing the initial interval between tetani, caused a more pronounced PCD. From these results it can be concluded that fatigue development and recovery are complex processes which cannot be readily explained by a sin

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08382.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Intracellular pH (pH,) has been measured before fatiguing stimulation and during recovery in single toe‐muscle fibres ofXenopusat room temperature. Liquid ion‐sensor microelectrodes were used for pH1measurements. The pH1measured before fatiguing stimulation was 6.93 ± 0.11 (mean ± SD,n= 9) in type 1 fibres and 6.99 ± 0.10 (n= 4) in type 2 fibres. About 1 min after tension had been suppressed to approximately 40% of the original by repeated tetanic contractions, pH, was measured again; it was then reduced to 6.34 ± 0.13 (range 6.15‐6.50) and 6.71 ± 0.17 (range 6.50‐6.85) in type 1 and type 2 fibres, respectively. The pH1recovered at a rate of about 0.05 pH units min‐1and was always normalized well before tension. Fibres which exhibited post‐contractile depression (PCD), a delayed force suppression during the recovery period, had similar pH1normalization rates to those of other fibres. The large variation in pH1values obtained in fibres fatigued to a standard tension level leads us to conlude that an intracellular acidification is not likely to be the major cause of fatigue produced by intermittent tetanic stimulation. However, an important inhibitory effect in the most acidified fibres, cannot be excluded. Furthermore, we conclude that force recovery in our experiments is controlled by factor

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1988.tb08383.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY