bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation by gastric acid of the processing of progastrin‐derived peptides in rat antral mucosa
Authors: Macro J. A. , Bate G. W. , Varro A. , Vaillant C. , Seidah N. G. , Dimaline R. , Dockray G. J. 
Published: September 2004

Inhibition of gastric acid secretion by proton pump inhibitors like omeprazole increases the synthesis and secretion of the pyloric antral hormone gastrin. We report here how omeprazole influences the conversion of the gastrin precursor to its final products, and the abundance of mRNAs encoding proteins associated with progastrin processing in rat antral mucosa.
Progastrin processing was studied using a pulse–chase protocol in antral mucosa, incubated in vitro, from rats treated with omeprazole for up to 5 days. Labelled peptides were detected by on–line scintillation counting after immunoprecipitation and HPLC. The mRNAs encoding prohormone‐processing enzymes were identified by Northern blot, polymerase chain reaction or ribonuclease protection assay, and their cellular origins identified by immunocytochemistry.
Cleavage of [3H]‐ and [35S]‐labelled progastrins at Arg‐94–95 or Arg‐57–58, and amidation at Phe‐92 were not influenced by pretreatment with omeprazole. In contrast, cleavage of G34 (the thirty‐four amino acid amidated gastrin) at Lys‐74–75 to give G17 (the seventeen amino acid amidated gastrin), and of G34–Gly to Gl7–Gly (G34 and G17 with COOH‐terminal glycine), was increased 3‐fold after treatment with omeprazole for either 1 or 5 days.
Approximately 20% of newly synthesized amidated and Gly‐extended gastrins were secreted within 240 min of the labelling period in omeprazole‐treated samples, but secretion of labelled gastrins from control tissue was undetectable over a comparable period.
The amidating enzyme, peptidylglycine α‐amidating mono‐oxygenase (PAM), the prohormone convertases PC1/3, PC2, PC5 and the PC2 chaperone 7B2 were localized to rat antral gastrin cells by immunocytochemistry. The relative abundance of mRNA species encoding 7B2, PC5 and PAM were unchanged after treatment with omeprazole for 5 days, whereas gastrin, PC1/3 and PC2 mRNAs are known to increase at this time.
The main consequence of increased cleavage at Lys‐74–75 is the production of G17 and G17–Gly at the expense of G34 and G34–Gly, respectively. The latter have longer plasma half‐lives, and so their increased cleavage may serve to limit the rise in plasma gastrin concentration after inhibition of acid secretion. Changes in the abundance of mRNAs encoding prohormone‐processing enzymes cannot account for the rapidity of the changes in cleavage of progastrin at Lys residues after omeprazole.
Effect of Cell Shrinkage on Permeability of Cultured Bovine Aortic Endothelia and Frog Mesenteric Capillaries
Authors: Kajimura M. , O'Donnell M. E. , Curry F. E. 
Published: September 2004

We have tested the hypothesis that a reduction in endothelial cell volume increases microvessel permeability and that the degree of endothelial cell attachment to their basement membranes determines the magnitude of permeability changes caused by a reduction in endothelial cell volume.
A decrease in endothelial cell volume was imposed on both intact microvessels and cultured endothelial monolayers by raising osmolarity by 100 mosmol l−1
We found that hypertonic solutions did not increase the hydraulic permeability (Lp) of individually perfused venular microvessels in frog mesentery when the perfusate contained albumin. Hypertonic solutions did increase Lp, however, after we perfused the microvessels with the peptide Gly‐Arg‐Gly‐Asp‐Thr‐Pro (GEGDTP; 0.3 mmol l−1), to disrupt integrin‐dependent endothelial cell (EC) attachment to the extracellular matrix (ECM).
After albumin was removed from the perfusate, hypertonic solutions increased Lp of microvessels and the permeability of endothelial monolayers to α‐lactalbumin.
Our findings indicate that endothelial cell integrin‐ECM binding plays a role in transducing changes in cell volume and/or shape into changes in permeability. We hypothesize that removal of albumin from the vascular perfusate may compromise EC–ECM interactions via an integrin‐dependent mechanism.
Mechanical study of rat soleus muscle using caged ATP and X‐ray diffraction: high ADP affinity of slow cross‐bridges
Authors: Horiuti K. , Yagi N. , Takemori S. 
Published: September 2004

The cross‐bridges in slow‐ and fast‐twitch fibres (taken, respectively, from soleus and psoas muscles of rats) were examined in mechanical experiments using caged ATP and X‐ray diffraction, to compare their binding of ATP and ADP.
Caged ATP was photolysed in rigor fibres. When ADP was removed from pre‐photolysis fibres, the initial relaxation (±Ca2+) in soleus was as fast as that in psoas fibres, whereas the subsequent contraction (+Ca2+) was slower in soleus than in psoas. The ATPase rate during the steady‐state contraction was also slower in soleus fibres.
When ADP was added to pre‐photolysis fibres (±Ca2+), tension developed even in the initial phase, the overall tension development being biphasic. Both initial and late components of the Ca2+‐free contraction were enhanced when ADP was added before photolysis, although pre‐photolysis ADP was not a prerequisite for the late component. The effect of ADP was greater in soleus than in psoas fibres. Static experiments on rigor fibres revealed a higher ADP affinity in soleus fibres.
The intensity of the actin layer‐line from ADP rigor soleus fibres decreased rapidly on photorelease of ATP. We conclude that, despite the tight ADP binding of the soleus cross‐bridge, its isometric reaction is not rate limited by the ‘off’ rate of ADP.
Role of Joint Receptors in Modulation of Inspiratory Intercostals Activity by Rib Motion in Dogs
Authors: De Troyer André 
Published: September 2004

Inspiratory activity in the canine external intercostal muscles is exquisitely sensitive to the direction and amplitude of the inspiratory displacement of the ribs. This study was designed to investigate the role of muscle receptors, in particular the muscle spindles, in mediating this phenomenon.
External intercostal inspiratory activity showed a reflex increase when the normal cranial motion of the ribs and the normal shortening of the muscles was reduced, and showed a reflex decrease when the cranial motion of the ribs and the shortening of the muscles was augmented. However, clamping the two ribs making up the interspace and maintaining muscle length constant only moderately attenuated these responses.
These persistent responses remained unchanged after section of the levator costae muscles.
The responses were attenuated but still present after section of the external intercostals in the contiguous segments and denervation of the internal intercostals.
These reflex responses are therefore mediated in part by non‐muscular receptors, which most likely lie within the costovertebral joints. These joint receptors might be a primary determinant of the load‐compensating reflex.
Chemo‐mechanical energy transduction in relation to myosin isoform composition in skeletal muscle fibres of the rat
Authors: Reggiani C. , Potma E. J. , Bottinelli R. , Canepari M. , Pellegrino M. A. , Stienen G. J. M. 
Published: September 2004

ATP consumption and force development were determined in single skinned muscle fibres of the rat at 12 °C. Myofibrillar ATPase consumption was measured photometrically from NADH oxidation which was coupled to ATP hydrolysis. Myosin heavy chain (MHC) and light chain (MLC) isoforms were identified by gel electrophoresis.
Slow fibres (n= 14) containing MHCI and fast fibres (n= 18) containing MHCIIB were compared. Maximum shortening velocity was 1.02 ± 0.63 and 3.05 ± 0.23 lengths s−1, maximum power was 1.47 ± 0.22 and 9.59 ± 0.84 W l−1, and isometric ATPase activity was 0.034 ± 0.003 and 0.25 ± 0.01 mM s−1 in slow and in fast fibres, respectively.
In fast as well as in slow fibres ATP consumption during shortening increased above isometric ATP consumption. The increase was much greater in fast fibres than in slow fibres, but became similar when expressed relative to the isometric ATPase rate.
Efficiency was calculated from mechanical power and free energy change associated with ATP hydrolysis. Maximum efficiency was larger in slow than in fast fibres (0.38 ± 0.04 versus 0.28 ± 0.03) and was reached at a lower shortening velocity.
Within the group of fast fibres efficiency was lower in fibres which contained more MLC3f. We conclude that both MHC and essential MLC isoforms contribute to determine efficiency of chemo‐mechanical transduction.
Is energy expenditure in the hamster primarily under homeostatic or circadian control?
Authors: Refinetti Roberto , Menaker Michael 
Published: September 2004

In order to discriminate between homeostatic and circadian control of energy expenditure, this paper considers whether a shorter circadian cycle will produce a proportional reduction in energy expenditure (so that expenditure per unit time is conserved) or alternatively whether energy expenditure will be compressed into the shorter cycle (so that energy expenditure per cycle is conserved). To answer this question, we measured energy expenditure in tau mutant hamsters (whose free‐running circadian period has been reduced to about 20 h by a single gene mutation) and wild‐type hamsters (whose free‐running circadian period is about 24 h).
In one experiment, the circadian rhythm of running‐wheel activity of tau mutant hamsters was compared with that of wild‐type hamsters. The rate of running was not affected by the mutation and, consequently, the total amount of activity per cycle was significantly less in mutants than in wild‐type hamsters, whereas the total amount of activity per unit time was nearly the same.
In a second experiment, we measured energy expenditure by indirect calorimetry. Metabolic rate was not affected by the mutation and, consequently, the total amount of energy expended per cycle was significantly less in mutants than in wild‐type hamsters but equivalent per unit time.
Because the amount of energy expenditure and locomotor activity was found to be proportional to the circadian cycle, we conclude that expenditure per unit time – rather than expenditure per circadian cycle – is conserved in the mutant animals. Therefore, we infer that energy expenditure in hamsters is primarily under homeostatic, not circadian, control. Further research is necessary to determine whether this inference can be applied to other species.
Spatial Patterns of Fasting and Fed Antropyloric Pressure Waves in Humans
Authors: Sun W. M. , Hebbard G. S. , Malbert C.‐H. , Jones K. L. , Doran S. , Horowitz M. , Dent J. 
Published: September 2004

Gastric mechanics were investigated by categorizing the temporal and spatial patterning of pressure waves associated with individual gastric contractions.
In twelve healthy volunteers, intraluminal pressures were monitored from nine side hole recording points spaced at 1.5 cm intervals along the antrum, pylorus and duodenum.
Pressure wave sequences that occurred during phase II fasting contractions (n= 221) and after food (n= 778) were evaluated.
The most common pattern of pressure wave onset along the antrum was a variable combination of antegrade, synchronous and retrograde propagation between side hole pairs. This variable pattern accounted for 42% of sequences after food, and 34% during fasting (P < 0.05). Other common pressure wave sequence patterns were: purely antegrade ‐ 29% after food and 42% during fasting (P < 0.05); purely synchronous ‐ 23% fed and 17% fasting; and purely retrograde ‐ 6% fed and 8% fasting. The length of sequences was shorter after food (P < 0.05). Some sequences ‘skipped’ individual recording points.
The spatial patterning of gastric pressure wave sequences is diverse, and may explain the differing mechanical outcomes among individual gastric contractions.
Better understanding of gastric mechanics may be gained from temporally precise correlations of luminal flows and pressures and gastric wall motion during individual gastric contraction sequences.
Maximum rate of oxygen uptake by human skeletal muscle in relation to maximal activities of enzymes in the Krebs cycle
Authors: Blomstrand Eva , Rådegran Göran , Saltin Bengt 
Published: September 2004

Ten subjects performed incremental exercise up to their maximum work rate with the knee extensors of one leg. Measurements of leg blood flow and femoral arteriovenous differences of oxygen were made in order to be able to calculate oxygen uptake of the leg.
The volume of the quadriceps muscle was determined from twenty‐one to twenty‐five computer tomography section images taken from the patella to the anterior inferior iliac spine of each subject.
The maximal activities of three enzymes in the Krebs cycle, citrate synthase, oxoglutarate dehydrogenase and succinate dehydrogenase, were measured in biopsy samples taken from the vastus lateralis muscle.
The average rate of oxygen uptake over the quadriceps muscle at maximal work, 353 ml min−1kg−1, corresponded to a Krebs cycle rate of 4.6 μmol min−1 g−1. This was similar to the maximal activity of oxoglutarate dehydrogenase (5.1 μmol min−1 g−1), whereas the activities of succinate dehydrogenase and citrate synthase averaged 7.2 and 48.0 μmol min−1 g−1, respectively.
It is suggested that of these enzymes, only the maximum activity of oxoglutarate dehydrogenase can provide a quantitative measure of the capacity of oxidative metabolism, and it appears that the enzyme is fully activated during one‐legged knee extension exercise at the maximal work rate.
Reflex cardiac dromotropic responses to stimulation of the carotid and aortic chemoreceptors in the anaesthetized cat
Authors: Jones James F. X. , Daly M. de Burgh 
Published: September 2004

The reflex changes in the dromotropic state of the heart (P–R interval or atrioventricular conduction time) in response to selective stimulation of the carotid and aortic bodies by sodium cyanide were studied in the anaesthetized cat. The heart was paced and the arterial blood pressure was kept constant to minimize secondary effects of changes in arterial baroreceptor activity.
Stimulation of the carotid and aortic bodies caused an increase in the atrioventricular conduction time.
Evidence is presented to suggest that this negative dromotropic response was due predominantly to a vagal cholinergic mechanism. There is a small sympathetic component but only in so far as the carotid body reflex is concerned.
The negative dromotropic responses were enhanced during reflex suppression of the central inspiratory neuronal drive combined with minimal activity of the slowly adapting pulmonary stretch afferents indicating that they are respiratory modulated.
The clinical implications of these results are discussed.
Actions of compounds manipulating the nitric Oxide system in the cat primary visual cortex
Authors: Cudeiro Javier , Rivadulla Casto , Rosa Rodriguez  , Grieve Kenneth L. , Martínez‐Conde Susana , Acuña Carlos 
Published: September 2004

We iontophoretically applied NG‐nitro‐L‐arginine (l‐NOArg), an inhibitor of nitric oxide synthase (NOS), to cells (n= 77) in area 17 of anaesthetized and paralysed cats while recording single‐unit activity extracellularly. In twenty‐nine out of seventy‐seven cells (38%), compounds altering NO levels affected visual responses.
In twenty‐five out of twenty‐nine cells, l‐NOArg non‐selectively reduced visually elicited responses and spontaneous activity. These effects were reversed by co‐application of l‐arginine (l‐Arg), which was without effect when applied alone. Application of the NO donor diethylamine‐nitric oxide (DEA‐NO) produced excitation in three out of eleven cells, all three cells showing suppression by l‐NOArg. In ten cells the effect of the soluble analogue of cGMP, 8‐bromo‐cGMP, was tested. In three of those in which l‐NOArg application reduced firing, 8‐bromo‐cGMP had an excitatory effect. In six out of fifteen cells tested, L‐NOArg non‐selectively reduced responses to NMDA and α‐amino‐3‐hydroxy‐5‐methylisoxasole‐4‐propionic acid (AMPA). Again, co‐application of l‐Arg reversed this effect, without enhancing activity beyond control values.
In a further subpopulation of ten cells, l‐NOArg decreased responses to ACh in five.
In four out of twenty‐nine cells l‐NOArg produced the opposite effect and increased visual responses. This was reversed by co‐application of l‐Arg. Some cells were also affected by 8‐bromo‐cGMP and DEA‐NO in ways opposite to those described above. It is possible that the variety of effects seen here could also reflect trans‐synaptic activation, or changes in local circuit activity. However, the most parsimonious explanation for our data is that NO differentially affects the activity of two populations of cortical cells, in the main causing a non‐specific excitation.
The effect of tetracaine on supontaneous Ca2+ release and sarcoplasmic reticulum calcium content in rat ventricular myocytes
Authors: Overend C. L. , Eisner D. A. , O'Neill S. C. 
Published: September 2004

The effects of tetracaine were studied on voltage‐clamped rat ventricular myocytes, which exhibited Ca2+ overload as identified by supontaneous Ca2+ release from the sarcoplasmic reticulum (SR) as shown by the associated contractions. This Ca2+ release was initially abolished by tetracaine before returning at a lower frequency, but greater amplitude, than the control. On removal of tetracaine, there was a burst of supontaneous Ca2+ release activity. All these effects were dose dependent, from 25 to 200 μm tetracaine.
The supontaneous Ca2+ release activated an inward Na+–Ca2+ exchange current as Ca2+ was pumped out of the cell. The integral of this current (i.e. the Ca2+ efflux) was increased in the presence of tetracaine. The calcium efflux per unit time was unaffected by tetracaine.
The SR Ca2+ content was increased by tetracaine, as shown by the integral of the caffeine‐evoked Na+–Ca2+ exchange current. The increase of SR Ca2+ content was equal to the extra Ca2+ lost from the cell during the burst on removal of tetracaine, and to estimates of the extra calcium gained over the quiescent period following addition of tetracaine.
It is concluded that partial inhibition of calcium‐induced calcium release increases SR Ca2+ content. In the steady state, cell Ca2+ balance is maintained as the lower frequency of supontaneous release (that activates efflux) is compensated for by their greater size.
Orally projecting interneurones in the guinea‐pig small intestine
Authors: Brookes S. J. H. , Meedeniya A. C. B. , Jobling P. , Costa M. 
Published: September 2004

Orally projecting, cholinergic interneurones are important in mediating ascending excitatory reflexes in the small intestine. We have shown that there is just one major class of orally projecting interneurone, which we have characterized using retrograde labelling in organ culture, combined with immunohistochemistry, intracellular recording and dye filling.
Orally projecting interneurones, previously shown to be immunoreactive for choline acetyltransferase, tachykinins, enkephalin, calretinin and neurofilament protein triplet, have axons up to 14 mm long and are the only class of cells with orally directed axons more than 8.5 mm long.
They are all small Dogiel type I neurones with short dendrites, usually lamellar in form, and a single axon which sometimes bifurcates. Their axons give rise to short varicose collaterals in myenteric ganglia more than 3 mm oral to their cell bodies.
Orally projecting interneurones receive prominent fast excitatory post synaptic potentials (fast EPSPs). A major source of fast EPSPs is other ascending interneurones located further aborally. They also receive fast EPSPs from circumferential pathways.
In the stretched preparations used in this study, orally projecting interneurones were highly excitable, firing repeatedly to depolarizing current pulses and had negligible long after ‐hyperpolarizations following their action potentials. They did not receive measurable non‐cholinergic slow excitatory synaptic inputs.
Ascending interneurones had a characteristic inflection in their membrane responses to depolarizing current pulses and their first action potential was typically delayed by approximately 30 ms. Under single electrode voltage clamp, ascending interneurones had a transient outward current when depolarized above –70 mV from more hyperpolarized holding potentials. Ascending interneurones also consistently showed marked inward rectification under both current clamp and voltage clamp conditions.
This class of cells has consistent morphological, neurochemical and electrophysiological characteristics and are important in mediating orally directed enteric reflexes.
Characterization of vagal pathways mediating gastric accommodation reflex in rats
Authors: Takahashi Toku , Owyang Chung 
Published: September 2004

We investigated the vagal pathways mediating the gastric accommodation reflex in the rat stomach.
Gastric distension (6 ml) evoked an increase of 9.0 ± 1.0 cm H2O of intragastric pressure in vivo. Pretreatment with tetrodotoxin (TTX) caused a significant pressure increase by gastric distension, reaching 17.0 ± 1.7 cm H2O, suggesting mediation by neural pathways.
The pressure increase evoked by gastric distension was significantly enhanced in vivo by acute truncal vagotomy (TV), hexamethonium (C6), and NG‐nitro‐L‐arginine methyl ester (l‐NAME), but not by vasoactive intestinal polypeptide (VIP) antiserum, guanethidine, or splanchnicotomy.
Gastric distension (6 ml) evoked a much larger intragastric pressure in the denervated, vascularly isolated, perfused rat stomach in vitro. Intra‐arterial application of TTX and l‐NAME did not cause further pressure increases evoked by gastric distension.
The pressure increase evoked by gastric distension remained high 2 weeks after TV in vivo. However, the accommodation reflex was fully restored 4 weeks after TV in vivo. This reflex was antagonized by TTX, C6 and l‐NAME, but not by VIP antiserum, guanethidine and splanchnicotomy.
Similar to in vivo studies, gastric distension caused a smaller increase in intragastric pressure in response to gastric distension in the denervated, vascularly isolated, perfused stomach obtained from rats 4 weeks after vagotomies in vitro. The pressure increase evoked by gastric distension was significantly enhanced by l‐NAME, hexamethonium and TTX.
It is suggested that the vago‐vagal reflex plays an important role in mediating the accommodation reflex. This involves a vagal efferent pathway that uses nitric oxide as a final neurotransmitter mediating gastric relaxation in intact rats. It is also suggested that the adaptive mechanism mediating the accommodation reflex following vagotomy occurs in the gastric myenteric plexus.