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The rests of Malassez and chronic marginal periodontitis.

The structure of the rests of Malassez and the relationship which they bear to the junctional epithelium in the marginal region of pigs' molars was investigated. A 3-dimensional picture of the marginal rests and their relationship to the junctional epithelium was built up by means of standardized photomicrographs made from serial sections. In teeth involved in chronic marginal inflammation, the rests in this region appeared to form a continuous network and we confirmed the original suggestion of Grant & Bernick that, at frequent intervals, the junctional epithelium"... seemed to be continuous with the epithelial rests in the upper third of the root...". If the anatomical relationship of the rests in man resembles that seen in the pig and they form a continuous network communicating at intervals with the junctional epithelium, this relationship must inevitably lead to speculation about the effects of any potential for reactive proliferative equivalent to that which is frequently seen in the apical region. It is possible that the rests might be acting as the "thin end of the wedge", augmenting and facilitating apical migration of the junctional epithelium during the pathogenesis of the periodontal pocket.

Animals↗

Noradrenaline spillover during exercise in active versus resting skeletal muscle in man.

Increases in plasma noradrenaline (NA) concentration occur during moderate to heavy exercise in man. This study was undertaken to examine the spillover of NA from both resting and contracting skeletal muscle during exercise. Six male subjects performed one-legged knee-extension so that all measurements could be made both in the exercising and in the resting leg. Subjects exercised for 10 min at each of 50% and 100% of the peak performance capacity of the leg. Leg blood flow was measured by thermodilution and blood samples were drawn for the determination of plasma NA and adrenaline, first in the resting leg and then in the exercising leg. To calculate NA spillover, the extraction of NA (NAe) or of adrenalin (Ae) is required: NAe was measured by repeating the experiment under constant [3H]NA infusion following a 40-min rest period. During exercise, NA spillover was significantly larger in the exercising leg than in the resting leg both during 50% and 100% leg exercise. These results suggest that contracting skeletal muscle may contribute to a larger extent than resting skeletal muscle to increasing the level of plasma NA during exercise. Contractile activity may influence the NA spillover from skeletal muscle by a presynaptic and/or postsynaptic influence on the sympathetic nervous activity to this tissue.

Adult↗

Transmural distribution of left ventricular glucose uptake in spontaneously hypertensive rats during rest and exercise.

The transmural distribution of glucose uptake was studied in the left ventricle of 6-month-old male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) during rest and swimming (20 min) using the 2-deoxyglucose method. The baseline mean arterial pressure was 128 +/- 8 (n = 8) in the WKY and 188 +/- 22 mmHg (n = 8) in the SHR (P less than 0.001). This pressure remained constant in the resting groups, whereas the product of mean arterial pressure and heart rate was initially 45 x 10(3) +/- 3 x 10(3) and 63 x 10(3) +/- 4 x 10(3) mmHg beats min-1 in the swimming WKY and SHR and increased by 34-48 x 10(3) mmHg beats min-1 during the swimming period. Total glucose uptake was 3.9 +/- 1.2 mumol min-1 g-1 protein in the resting WKY rats and 1.4 +/- 0.4 mumol min-1 g-1 protein (P less than 0.001) in the swimming ones, the corresponding values for the resting and swimming SHR being 4.8 +/- 1.4 mumol min-1 g-1 protein and 3.2 +/- 1.2 mumol min-1 g-1 protein (P less than 0.01). Glucose uptake was 30% greater in the subendocardium (ENDO) of the resting WKY than in the subepicardium (EPI) (P less than 0.01), but this gradient disappeared during swimming. Glucose uptake in the resting SHR was greatest in the middle layer of the ventricular wall, with no difference between ENDO and EPI, whereas during swimming the glucose uptake was distributed evenly across the left ventricular wall. The blood lactate/pyruvate ratio increased only transitorily during the first minutes in the swimming SHR, while their plasma free fatty acid concentration was 1.2-1.3 mM initially and decreased by 32% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Exercise thermoregulation with bed rest, confinement, and immersion deconditioning.

Altered thermoregulation following exposure to prolonged (12-14 days) of bed rest and 6 hr of head-down thermoneutral water immersion in humans, and cage confinement (8 weeks) in male, mongrel dogs resulted in occasional increased core temperature (Tcore) at rest, but consistent "excessive" increase in Tcore during submaximal exercise. This excessive increase in Tcore in nonexercising and exercising subjects was independent of the mode (isometric or isotonic) of exercise training during bed rest, and was associated with the consistent hypovolemia in men but not in women taking estrogen supplementation (1.25 mg premarin/ day) which restored plasma volume during bed rest to ambulatory control levels. Post-bed rest exercise sweating (evaporative heat loss) was unchanged or higher than control levels; however, calculated tissue heat conductance was significantly lower in men, and forearm venoconstriction was greater (venous volume was reduced) in women during exercise after bed rest. Because sweating appeared proportional to the increased level of Tcore, these findings suggest that one major factor for the excessive hyperthermia is decreased core to periphery heat conduction. Exercising dogs respond like humans with excessive increase in both rectal (Tre) and exercising muscle temperatures (Tmu) after confinement and, after eight weeks of exercise training on a treadmill following confinement, they had an attenuated rate of increase of Tre even below ambulatory control levels. Intravenous infusion of glucose also attenuated not only the rise in Tre during exercise in normal dogs, but also the excessive rise in Tre and exercising Tmu after confinement. Oral glucose also appeared to reduce the rate of increase in excessive Tre in men after immersion deconditioning. There was a greater rate of rise in Tcore in two cosmonauts during supine submaximal exercise (65% VO2 max) on the fifth recovery day after the 115-day Mir 18 mission. Thus, the excessive rise in core temperature after deconditioning appears to be caused by decreased peripheral vasodilation in humans. Factors related to glucose metabolism may influence this mechanism.

Adaptation, Physiological↗

Tension due to interaction between the sliding filaments in resting striated muscle. The effect of stimulation.

1. A resting sartorius muscle of the frog or toad possesses a special kind of elasticity which is shown to be due to a component lying between the two sets of filaments. The elastic effect is seen only for very small length changes, up to about 0.2% of the muscle length, and the ;elastic limit' is then reached. If the length change then continues at a constant velocity the tension developed is maintained at a fixed level, producing a sort of frictional resistance. The component responsible is called the ;short-range elastic component', or SREC.2. It is also shown that a small part of the permanent tension of a resting muscle is probably due to ;active' interaction between the filaments. This is called the ;filamentary resting tension', or FRT. For a sarcomere length of 2.0 mu the FRT amounts to about 150 mg in a muscle weighing 100 mg.3. The stiffness of the SREC and the magnitude of the FRT are shown to be related to one another. They are both increased, and may rise to high values, by making the external solution hypertonic.4. The working hypothesis is as follows. In a resting muscle the cross-bridges on the myosin filaments are not entirely inactive, but a very small proportion of them are cross-linked with the actin filaments. The links are very stable and have a long ;life'. The elastic behaviour is due to the flexural rigidity, or spring-like properties of these bridges. The elasticity is ;short-range' because the bridges can be bent, or stretched, only a small way from the steady-state position before the contacts ;slip'. The ;filamentary resting tension' (which is present in the absence of any external length change) is attributed to an ;active process', which operates by imparting ;organized' potential energy to the participating cross-bridges, by potentiating their attachment, against their elastic resistance, to sites on the actin filaments which are displaced towards the Z line.5. It is shown that the ability of the muscle to maintain a ;frictional' resistance to a continuing, slow, length change is suppressed during a maintained tetanic contraction. The process of suppression starts during the period of the latency relaxation.6. It is suggested that the latency relaxation may be due to a reduction of the filamentary resting tension.7. The experiments with the latency relaxation were facilitated by the use of strongly hypertonic solutions. The positive twitch tension is then greatly reduced, or may be practically abolished, while the latency relaxation remains at about its normal size and is extended in duration.

Animals↗

The resting potential of moth muscle fibre.

1. The membrane of the moth muscle fibre was tested for resting permeability to various ions: it is not permeable to Mg(2+) or Ca(2+); it is slightly permeable to Na(+) and NH(4) (+); it is appreciably permeable to Cl(-), but Cl(-) is passively distributed; it is apparently permeable to H(+) but effects of HCO(3) (-) are not ruled out; and it is primarily permeable to K(+).2. Measurement of the internal K(+) activity showed that E(K) is less negative than the resting potential.3. In the presence of DNP, or under anoxia, the membrane potential approaches, E(K); there is a small concomitant decrease in effective membrane resistance.4. An increase in external Ca(2+) concentration is accompanied by increased effective membrane resistance and an increase in amplitude of the negative resting potential.5. Cooling the membrane (below room temperature) decreased the amplitude of the resting potential by 4-16 mV per 10 degrees C, and was accompanied by a large increase in effective membrane resistance.6. The experimental results most readily fit the hypothesis that the resting potential of the moth muscle fibre, although the membrane is highly permeable to K(+), Cl(-) and apparently to H(+), is primarily maintained by an electrogenic transport process which generates an ionic current across the membrane. The possibility that the concentration gradient of H(+) ions is metabolically maintained at a level sufficient to explain the resting potential was considered to be unlikely but could not be directly excluded.

Acetazolamide↗

Transient, steady-state and rebreathing responses to carbon dioxide in man, at rest and during light exercise.

1. The transient ventilatory response to CO2, measured using short pulses at constant inflow, was compared with the steady-state response at rest and during exercise at 50 W, and with the rebreathing response at rest, in nine healthy subjects. At rest CO2 was given at flow rates of 0.2 and 0.4 l min-1 and during exercise, to compensate for the smaller inhaled CO2 fraction as ventilation increased, at flow rates of 0.4 and 0.8 l min-1. 2. We calculated two indexes of gain for the transient response: the ratio of the peaks of the ventilation and PCO2 pulses, and the ratio of their integrals. 3. The steady-state response was greater than the transient response at rest and during exercise, but there was no correlation between the two. The rebreathing response was greater than both. Both the transient and the steady-state responses were greater during exercise than at rest. 4. To assess alinearity, the steady-state responses to the two CO2 flow rates were compared. At rest, there was no significant difference. During exercise, the response was greater to 0.4 than 0.8 l min-1, indicating alinearity concave downwards. 5. We conclude that the transient response as we calculate it is not representative of steady-state gain, and that the CO2 response in light exercise is steeper, and concave downwards in shape. The rebreathing technique overestimates CO2 sensitivity near the control point.

Adult↗

The pool of ADP and ATP regulates anaerobic product formation in resting cells of Lactococcus lactis.

Lactococcus lactis grows homofermentatively on glucose, while its growth on maltose under anaerobic conditions results in mixed acid product formation in which formate, acetate, and ethanol are formed in addition to lactate. Maltose was used as a carbon source to study mixed acid product formation as a function of the growth rate. In batch and nitrogen-limited chemostat cultures mixed acid product formation was shown to be linked to the growth rate, and homolactic fermentation occurred only in resting cells. Two of the four lactococcal strains investigated with maltose, L. lactis 65.1 and MG1363, showed more pronounced mixed acid product formation during growth than L. lactis ATCC 19435 or IL-1403. In resting cell experiments all four strains exhibited homolactic fermentation. In resting cells the intracellular concentrations of ADP, ATP, and fructose 1,6-bisphosphate were increased and the concentration of P(i) was decreased compared with the concentrations in growing cells. Addition of an ionophore (monensin or valinomycin) to resting cultures of L. lactis 65.1 induced mixed acid product formation concomitant with decreases in the ADP, ATP, and fructose 1,6-bisphosphate concentrations. ADP and ATP were shown to inhibit glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and alcohol dehydrogenase in vitro. Alcohol dehydrogenase was the most sensitive enzyme and was totally inhibited at an adenine nucleotide concentration of 16 mM, which is close to the sum of the intracellular concentrations of ADP and ATP of resting cells. This inhibition of alcohol dehydrogenase might be partially responsible for the homolactic behavior of resting cells. A hypothesis regarding the level of the ATP-ADP pool as a regulating mechanism for the glycolytic flux and product formation in L. lactis is discussed.

Adenosine Diphosphate↗

Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes.

Resting CD4+ T-cell populations from human immunodeficiency virus type 1 (HIV-1)-infected individuals include cells with integrated HIV-1 DNA. In individuals showing suppression of viremia during highly active antiretroviral therapy (HAART), resting CD4+ T-cell populations do not produce virus without cellular activation. To determine whether the nonproductive nature of the infection in resting CD4+ T cells is due to retroviral integration into chromosomal regions that are repressive for transcription, we used inverse PCR to characterize the HIV-1 integration sites in vivo in resting CD4+ T cells from patients on HAART. Of 74 integration sites from 16 patients, 93% resided within transcription units, usually within introns. Integration was random with respect to transcriptional orientation relative to the host gene and with respect to position within the host gene. Of integration sites within well-characterized genes, 91% (51 of 56) were in genes that were actively expressed in resting CD4+ T cells, as directly demonstrated by reverse transcriptase PCR (RT-PCR). These results predict that HIV-1 sequences may be included in the primary transcripts of host genes as part of rapidly degraded introns. RT-PCR experiments confirmed the presence of HIV-1 sequences within transcripts initiating upstream of the HIV-1 transcription start site. Taken together, these results demonstrate that HIV-1 genomes reside within actively transcribed host genes in resting CD4+ T cells in vivo.

Antiretroviral Therapy, Highly Active↗

Improvement of stress LVEF rather than rest LVEF after coronary revascularisation in patients with ischaemic cardiomyopathy and viable myocardium.

OBJECTIVE: To evaluate prospectively the response of left ventricular ejection fraction (LVEF) to high dose dobutamine infusion in patients showing substantial viability, with and without improved resting LVEF after revascularisation. METHODS: Before and 9-12 months after revascularisation, 50 patients with ischaemic cardiomyopathy (LVEF 32 (8)%) and substantial myocardial viability (> or = 4 viable segments) underwent radionuclide ventriculography and dobutamine stress echocardiography. Patients were divided into group 1, patients with, and group 2, patients without significant improvement in resting LVEF (> or = 5% by radionuclide ventriculography) after revascularisation. The response of LVEF during dobutamine stress echocardiography was compared in these two groups. RESULTS: Groups 1 and 2 were comparable in baseline characteristics, resting LVEF, and number of viable segments (mean (SD) 7 (4) v 6 (2), not significant). After revascularisation, the LVEF response during dobutamine stress echocardiography improved significantly in both groups (group 1, 34 (10)% to 56 (8)%; group 2, 32 (10)% to 46 (11)%; both p < 0.001). Interestingly, although resting LVEF did not improve in group 2, peak stress LVEF after revascularisation did (p < 0.001). Group 1 patients had, however, a greater increase in peak stress LVEF (group 1, 22 (10)%; group 2, 13 (9)%; p < 0.01). New York Heart Association and Canadian Cardiovascular Society classes decreased in both groups. CONCLUSIONS: Although patients with viable myocardium did not always have improved rest LVEF after revascularisation, peak stress LVEF improved. Assessment of improvement of resting function may not be the ideal end point to evaluate successful revascularisation.

Blood Pressure↗

Haemodynamic adaptation at rest and during exercise to long-term antihypertensive treatment with combination of beta-receptor blocking and vasodilator agent.

Systemic and pulmonary haemodynamics were studied at rest in the supine and upright position, and during exercise in the sitting position at 75 and 150 Watt, in 13 hypertensive men aged 50-8 +/- 8-7 years before and after 13 months treatment with oral oxprenolol (120 to 160 mg t.i.d.) supplemented by oral hydrallazine (50 to 75 mg t.i.d.) during the last 6 months. Pressures were recorded by means of catheters inserted percutaneously into the pulmonary and brachial artery; cardiac output was determined according to Fick. Treatment resulted in a significant reduction of systemic systolic, diastolic, and mean pressures at rest in the supine position and during exercise, and of systolic pressures in the upright posture. Pulmonary systolic and mean pressures increased slightly at rest in the supine position and during exercise, and no changes occurred at rest in the upright position. The left ventricular filling pressure was unchanged at rest both in the supine and upright position; it increased slightly during exercise. The haemodynamic changes by which systemic pressure was reduced were those typical of beta-adrenergic blockade: reduction of cardiac output resulting from a decrease of both heart rate and stroke volume, while the total systemic vascular resistance was unchanged at rest in the supine position but increased in the upright posture and during exercise. The A-V O2 difference increased remarkably. This long-term observation again suggests that the acute haemodynamic effects of an antihypertensive regimen can be modified during long-term application. It did not give evidence of a readjustment of the vascular resistance occurring, at least not in the upright position and during exercise, as has been suggested for long-term beta-adrenergic blockade.

Adult↗

Effect of oral propranolol on rest and exercise left ventricular ejection fraction, volumes, and segmental wall motion in patients with angina pectoris. Assessment with equilibrium gated blood pool imaging.

The effect of oral propranolol on left ventricular ejection fraction, left ventricular volumes, cardiac output, and segmental wall motion was assessed with multigated blood pool imaging both at rest and during supine exercise in 15 patients with angina pectoris. Propranolol had no effect on resting left ventricular ejection fractions. Before propranolol, they did not change during exercise, whereas after propranolol the ejection fractions increased slightly. Exercise left ventricular ejection fractions increased with propranolol in three patients with resting left ventricular ejection fractions of less than 40 per cent. More specifically, left ventricular end-diastolic volume index, end-systolic volume index, stroke volume index, and cardiac index were not altered significantly at rest or during exercise by propranolol. Exercise left ventricular ejection fractions were increased in five and unchanged in eight patients by propranolol. Those patients with increases in left ventricular ejection fractions had a greater change in left ventricular end-diastolic volume indices and a greater change in left ventricular end-systolic volume indices during exercise while on propranolol. Left ventricular segmental wall motion was not altered significantly during exercise by propranolol. We conclude that: (1) Left ventricular functional responses to propranolol during exercise are heterogeneous and not easily predicted; (2) propranolol causes no consistent deterioration in exercise left ventricular ejection fraction even in patients with resting ventricular ejection fractions less than 40 per cent; (3) increased exercise left ventricular ejection fraction with propranolol is contributed to by significant increases in end-diastolic volume during exercise; and (4) gated blood pool imaging is a useful method for characterising rest and exercise left ventricular ejection fractions and left ventricular volumes during propranolol therapy.

Adult↗

Value of the resting 12 lead electrocardiogram and vectorcardiogram for locating the accessory pathway in patients with the Wolff-Parkinson-White syndrome.

The resting 12 lead electrocardiogram and vectocardiogram were reviewed in 47 patients with the Wolff-Parkinson-White syndrome (a) who had pre-excitation on the resting 12 lead electrocardiogram, (b) who had a single anterograde conducting accessory pathway assessed and located during preoperative electrophysiological study and during epicardial mapping at operation, and (c) in whom surgical division of the accessory pathway resulted in loss of pre-excitation. The site of the accessory pathway established during operation was compared with that established by evaluating the polarity of the delta wave and QRS complex on the resting 12 lead electrocardiogram. The electrocardiogram was assessed by the Rosenbaum criteria (Wolff-Parkinson-White type A, left-sided pathway; or type B, right-sided pathway), the Gallagher criteria (atrial pacing resulting in maximal pre-excitation), and the World Health Organisation criteria (a composite of previous studies). The Gallagher and World Health Organisation criteria were derived from patients demonstrating maximal pre-excitation that often required atrial pacing. The present study was designed to determine whether these criteria could be accurately applied to the resting 12 lead electrocardiogram on which the degree of pre-excitation was variable. The Rosenbaum criteria correctly identified a left sided accessory pathway in 26 of 34 patients and a right-sided accessory pathway in nine of 13 patients. The Gallagher and World Health Organisation criteria correctly identified the location in only 15 (32%) of the 47 patients. The resting vectorcardiogram was inaccurate for locating the accessory pathway. Although published criteria are useful for identifying the site of the accessory pathway from an electrocardiogram obtained when rapid atrial pacing is being used to achieve maximal pre-excitation, they are not suitable for identifying the exact site of an accessory pathway from the resting 12 lead electrocardiogram.

Adolescent↗

Distribution of rest days in 12 hour shift systems: impacts on health, wellbeing, and on shift alertness.

OBJECTIVES: To investigate of the effects of distribution of rest days in 12 hour shift systems. Although several studies have examined the effects of compressing work schedules by comparing 8 and 12 hour shift systems, there is little published research examining the various forms of 12 hour shift system. METHODS: An abridged version of the standard shiftwork index which included retrospective alertness ratings was completed by a large sample of industrial shiftworkers. The respondents worked 12 hour shift systems that either did or did not incorporate breaks of > 24 hours between the blocks of day and night shifts. For the purposes of the analysis, each of these two groups were further subdivided into those who started their morning shift at 0600 and those who started at 0700. RESULTS: Systems which incorporated rest days between the day and night shifts were associated with slightly higher levels of on shift alertness, slightly lower levels of chronic fatigue, along with longer sleep durations when working night shifts and between rest days. Early changeovers were associated with shorter night sleeps between successive day shifts, but longer and less disturbed day sleeps between night shifts. These effects of changeover time were broadly in agreement with previous research findings. CONCLUSIONS: The distribution of rest days in 12 hour shift systems had only limited effects on the outcome measures, although the few modest differences that were found favoured systems which incorporated rest days between the day and night shifts. It is conceded that the design of the study may have obscured some subtle differences between the shift systems. Nevertheless, it is concluded that the impact of distribution of rest days seems to be minor relative to previously found effects of other features of shift systems--for example, shift duration.

Adult↗

Atrioventricular block in low potassium and K dependence of the nodal resting potential.

A progressive conduction block leading to atrioventricular dissociation develops in perfused rabbit hearts within 20-30 min of exposure to Krebs containing 0.5 mM potassium (low K). A decrease in potassium permeability resulting in membrane depolarization (as seen in Purkinje fibers) could be responsible for the loss of excitability in nodal cells. We investigated the K dependence of the resting potential and the long-term effects of low K perfusion on the resting and action potentials of nodal cells in rabbit hearts. The resting potential of atrial, atrionodal, and nodal cells varied by 52, 41, and 34 mV per decade of change in Ko within the range of 5-50 mM K. Hyperpolarization of the resting membrane, a progressive decline in action potential amplitude, and a decrease in maximum rate of rise were observed in nodal fibers when exposed to low K. Loss of propagated activity occurred in the middle node within 20-30 min while the cells remained hyperpolarized. There was no evidence of electrogenic Na extrusion and it seems that the low nodal resting potential results from a high resting PNa/PK permeability ratio. The early decrease in rate of rise in low K probably reflects an increase in K-dependent outward currents, whereas the progressive deterioration and final loss of conducted electrical activity may result from an accumulation of internal Na and Ca overload produced by low K inhibition of the Na pump.

Action Potentials↗

Influence of physical activity and dietary restraint on resting energy expenditure in young nonobese females.

An understanding of the physiological and behavioral determinants of resting energy requirements is important to nutritional considerations in females. We examined the influence of endurance training and self-reported dietary restraint on resting metabolic rate and fasting plasma hormones in 44 nonobese females characterized for body composition, maximal aerobic power (VO2 max), and daily energy intake. To examine the association of metabolic rate and dietary restraint with hormonal status, fasting plasma levels of insulin, glucose, and thyroid hormones (total and free fractions of thyroxine and triiodothyronine) were determined. In univariate analysis, resting metabolic rate (kcal.min-1) was positively related to VO2 max (L.min-1) (r = 0.54; p less than 0.01). This relationship, however, was partially dependent on body size, since fat-free mass was also related to resting metabolic rate (r = 0.42; p less than 0.01) and VO2 max (L.min-1) (r = 0.75; p less than 0.01). After controlling for fat-free weight using partial correlation analysis, the relation between RMR and VO2 max was weaker but controlling for fat-free weight using partial correlation analysis, the relation between RMR and VO2 max was weaker but still significant (partial r = 0.38; p less than 0.05). On the other hand, high levels of dietary restraint were associated with higher levels of body fat (r = 0.31; p less than 0.05) and a lower resting metabolic rate (r = -0.29; p = 0.07). These associations persisted after control for differences in fat-free mass. Total energy intake as well as total and free levels of triiodothyronine were not related to resting metabolic rate or level of dietary restraint.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Regulation of intracellular pH in resting and in stimulated parietal cells.

Microspectrofluorimetry of the pH-sensitive, fluorescent dye 2',7'-biscarboxyethyl-5 (6)-carboxyfluorescein (BCECF) was used to measure intracellular pH (pHi) in single parietal cells (PC) of intact rabbit gastric glands during resting and stimulated conditions. In 61% of PC, histamine plus isobutylmethylxanthine (IBMX) (both 100 microM) caused a small increase in pHi, ranging from 0.04 to 0.21 pH units (average delta pHi = 0.09 +/- 0.04 units over a 6-min period). In the other 39% of PC, pHi remained constant or decreased slightly (maximum decrease was 0.10 unit). The specific inhibitors omeprazole (50 microM, blocks H+- K+-ATPase), 4,4'-diisothiocyanodihydrostilbene-2,2'-disulfonic acid (H2DIDS; 100-200 microM, blocks Cl-HCO3 exchange) and amiloride (1 mM, blocks Na-H exchange) were added to both resting and stimulated PC. In stimulated PC, omeprazole caused pHi to decrease by 0.08 unit, but this inhibitor had no effect on pHi of resting PC. H2DIDS caused pHi to increase in stimulated PC five times faster compared with resting PC. Amiloride or Na-free solution (which should reverse the Na-H exchanger and cause cellular acidification) caused pHi to decrease 2.5 or 5 times, respectively, more slowly in stimulated PC compared with resting PC. Also, recovery from NH4-induced acidification (due primarily to Na-H exchange) was 1.8 times faster (measured at pHi 6.7) in resting vs. in stimulated PC. During histamine plus IBMX-induced stimulation, increased H secretion by the H+-K+-ATPase at the apical membrane is accompanied by an increase in activity of the Cl-HCO3 exchanger at the serosal membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

Myosin-product complex in the resting state and during relaxation of smooth muscle.

Previous findings suggested that in resting smooth muscle ADP is bound to myosin and that phosphorylation of the myosin, and its subsequent interaction with actin, increases the rate of ADP release. We have now extended these studies to include measurements of bound Pi as well as bound ADP in permeabilized rabbit portal vein. We report that in resting smooth muscle that has been exposed to [3H]ATP and [gamma-32P]ATP, followed by a chase in an unlabeled relaxing solution, the ratio of bound [3H]ADP to bound [32P]Pi is close to unity, and both are released at approximately the same rate. This suggests that myosin exists predominantly with both ADP and Pi bound under resting conditions and that the release of one is quickly followed by the release of the other. In contrast, there is a significant 30% excess of bound Pi over ADP in a muscle during relaxation from an isometric contraction. Under these conditions, while force output is slowly decreasing, both light chain phosphorylation and adenosinetriphosphatase (ATPase) activity have decreased to near-resting values. The time course of relaxation is similar to the time course of Pi release from both the resting and relaxing muscle. We propose that during relaxation the dephosphorylated cross bridges which are bearing force have Pi but not ADP bound and that detachment of the cross bridge (and thus force decay) is limited by Pi release from myosin which occurs at the same rate as in the resting muscle.

Adenosine Diphosphate↗