摘要:

This paper provides a broad review of the topic, but particularly emphasizes the definition of genetic factors that may cause interethnic differences in the capacity to metabolize drugs and toxic chemicals and recent case studies of dehydrogenases and mixed function oxidases.

ISSN:0008-4212    

DOI:10.1139/y82-001

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

Rat interscapular brown adipose tissue (IBAT) was homogenized to release the noradrenergic vesicles present in its dense sympathetic innervation. The vesicles were then studied by several sedimentation techniques using noradrenaline (NA) and dopamine β-hydroxylase (DBH) as markers. Sixty-three percent of the DBH activity and 29% of the NA in homogenates (0.25 Msucrose, 5 mMTris, pH 7.4 at 21 °C) of IBAT from 28 °C acclimated rats sedimented in the microsomal fraction (226 600 × gmax, 60 min). Differential sedimentation of the microparticulate DBH in a low-speed supernatant fraction of the homogenate indicated at least two distinct populations of microparticles with average sedimentation coefficients of 80 ± 11 and(4 °C) and containing, respectively, about 65 and 35% of the sedimentable DBH. Upon isopycnic, sucrose density centrifugation of the resuspended microsomal fraction, DBH peaked at a density of 1.091 but extended as a broad shoulder up to a density of about 1.19. During rate zonal centrifugation of the resuspended microsomal fraction on sucrose density gradients, microparticulate DBH and NA separated into slow and fast moving components. The modal density of the slow moving component upon isopycnic recentrifugation was 1.092, while the fast moving one, similarly treated, became almost equally distributed over a range of densities from 1.12 to 1.19. For the slow moving component, NA and DBH relative to protein were, respectively, 6.5 and 23 times more concentrated than in the IBAT homogenate. On the basis of its measured sedimentation characteristics, the slow moving component would correspond to vesicles having a calculted diameter of 66 nm. The data thus indicate that in IBAT, DBH and NA can be separated into two distinct populations of sedimentable particles. Whether or not these correspond to the small and large dense-cored vesicles observed by ultramicroscopy of IBAT remains to be demonstrated.

ISSN:0008-4212    

DOI:10.1139/y82-002

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

The subepicardial capillaries were visualised under normoxemia and hypoxemia by cinemicrophotography of the beating heart in open-chest rats. The functional intercapillary distances (ICD) were directly measured from focused frames. Under normoxemia, the average ICD was 19.2 μm and under hypoxemia, 17.9 μm (p < 0.01). This decrease of 1.3 μm under hypoxemia corresponds to an average recruitment of an additional 416 capillaries/mm2(from 2762 to 3178).During postnatal development, both the normoxemic and hypoxemic ICD's increased with left ventricular weight. The regression analysis of this relationship indicates that the hypoxemic ICD's remain significantly shorter within the observed range.In heterotopicall y isotransplanted, empty, beating rat hearts, there was no difference in functional ICD between normoxemia and hypoxemia either in 1-day-old (18.5 versus 18.6 μm) or in 7-day-old (17.1 versus 17.1 μm) transplants.Unlike the hearts in situ which could be observed only through a long working distance, low power objective (11×), the heterotopic transplants could also be observed through a higher power (22×) lens with an optical penetration of less than 5 μm. On the same hearts almost identical ICD's were obtained by both lenses during normoxemia and hypoxemia. Therefore, recruitment of capillaries observed on the normal hearts could not be due to different optical characteristics of the hypoxemic myocardium.

ISSN:0008-4212    

DOI:10.1139/y82-003

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

Inotropic responses to cumulative additions of methoxaminc (10−7to 3 × 10−4 M), isoproterenol (10−9to 10−5 M), or calcium (2 to 32 mM) were measured in isolated rat left atria and papillary muscles and rabbit right ventricular papillary muscles at three stimulation frequencies. Cardiac muscles were incubated in oxygenated Chenoweth–Koelle solution (2 mMcalcium) at 37 °C. The basal developed force (BDF) before and maximum developed force (MDF) after challenge with methoxamine and isoproterenol were inversely related to stimulation frequency in rat preparations. BDF was directly related to stimulation rate in rabbit papillary muscles while MDF was independent of the rate. Drug-induced increases in force (MDF – BDF) were independent of stimulation frequency in rat and inversely related to stimulation frequency in rabbit. Responses to calcium were similar to the observed adrenergic responses. Also, force–frequency relationships of the rat and rabbit preparations were not similar in the absence and presence of these agonists. These data show that inotropic responses by rat and rabbit hearts are not affected similarly by stimulation frequency and this may reflect a species difference in the utilization of extracellular calcium for contraction.

ISSN:0008-4212    

DOI:10.1139/y82-004

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

A peripheral nerve autograft placed on the surface of a normally innervated muscle has been shown to induce acetylcholine hypersensitivity and myofibrillar degeneration. Using a similar preparation, we determined the acid protease, alkaline protease, andN-acetylglucosaminidase activity in rat soleus muscle and the effect of protease inhibitors on these enzymes. Three days after nerve transplant, the muscle showed a significant increase in all three enzymes assayed. The protease inhibitors leupeptin and pepstatin totally prevented the nerve-induced increase in hydrolase activity. Our data suggest that muscle degeneration is secondary to an inflammatory response induced by the nerve.

ISSN:0008-4212    

DOI:10.1139/y82-005

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

The effects of Ba2+ions on twitches. K+-induced contractures, and on intracellularly recorded membrane potentials (Em) and depolarizations of frog skeletal muscle fibres were investigated. Exposure of toe muscles to choline–Ringer's solution with 10−3 MBa2+with Ca2+(1.08 mM) eliminated or very greatly reduced contractures produced by 60 mMK+. In contrast, not only did the same concentration of Ba2+ions fail to depress the twitch tension of isolated semitendinosus fibres when added to Ringer's with Ca2+, but it even restored twitches that had been eliminated in a zero Ca2+Ringer's solution. The restingEmof sartorius muscle fibres in choline–Ringer's solution was reduced about 20 mV by 10−3 MBa2+. This Ba2+ion concentration also antagonized the K+-induced depolarization. Thus in the presence of 1 mMBa2+, 20 mMK+hyperpolarized rather than depolarized the fibres and 60 or 123 mMK+produced only very slowly developing, small depolarizations. These results suggest that the loss of the K+-induced contracture in choline–Ringer's caused by Ba2+ions is due to an inhibition of the K+-induced depolarization. The latter result is consistent with previous findings of other workers that Ba2+ions block membrane K+channels.not available

ISSN:0008-4212    

DOI:10.1139/y82-006

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

Theory predicts that the membrane potential will polarize membrane molecules and cause them to vibrate coherently at a frequency of ~ 1011 Hz. If the supply of metabolic energy exceeds a minimum value, membrane phonons may condense their momentum into a single "giant" vibrational mode. At 1011 Hz ionic screening is small up to distances of approximately a micrometre, so forces of a range several orders of magnitude longer than chemical forces can arise. These forces may be attractive or repulsive depending on frequency. They should occur in every metabolically active membrane and may control macromolecular transport and enzyme–substrate interactions. We find that normal human erythrocytes in plasma form rouleaux faster than Brownian motion predicts. When cells are fixed in glutaraldehyde or are metabolically depleted, or if the membrane potential is brought to zero, the rate of aggregation agrees with Brownian theory. When the metabolically depleted cells are revived or if the membrane potential is restored, then the interaction returns.

ISSN:0008-4212    

DOI:10.1139/y82-007

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

Ammonia labeled with cyclotron-produced13N was injected intravenously in rats and the content of13N in 14 major organs and tissues was determined at eight intervals ranging from 0.2 to 50 min after injection. The distribution of13N at 12 s was employed to estimate the unidirectional tissue extraction for ammonia. The estimated fractional extraction for most of the tissues studied ranged from 70 to 100%. The 12-s13N concentrations in a number of tissues (with lungs and brain the principal exceptions) were found to be quite similar to those reported for42K+and86Rb+in the rat, suggesting a similar mechanism of transcapillary extraction. Most of the injected dose was initially extracted by the musculature, kings, and kidneys. The lungs and kidneys released the bulk of their extracted ammonia-derived nitrogen within 10 min of injection. The gut, heart, and spleen also recirculated extracted nitrogen, but on a much smaller scale than the lungs and kidneys. The recirculated label was accumulated mainly by muscle, liver, and skin. The results suggest that the lungs and kidneys are important sources of systemically recirculated ammonia metabolites in the rat.

ISSN:0008-4212    

DOI:10.1139/y82-008

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

Recent studies have shown thatN-nitroso compounds can activate arterial guanylate cyclase and relax isolated arterial smooth muscle; however, the effects of these substances on the cardiovascular system in the anesthetized cat are unknown. The present study was undertaken to compare the effects of several nitrosoguanidines and a nitrosamine,N-nitrosodimethylamine, on arterial guanylate cyclase activity, isolated arterial smooth muscle tone, and systemic vascular resistance in the anesthetized cat. Intravenous injections and infusions of the nitrosoguanidines glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) decreased systemic arterial pressure. During intravenous infusion of the nitrosoguanidines GTN and SNP, cardiac output was unchanged at the peak of the decrease in aortic pressure, indicating that the nitrosoguanidines GTN and SNP both reduced systemic vascular resistance. In addition, intraarterial injections of the nitrosoguanidines produced dose-dependent decreases in perfusion pressure in the feline mesenteric vascular bed perfused at constant flow. These substances were potent relaxants of isolated arterial smooth muscle and markedly activated arterial guanylate cyclase. In contrast,N-nitrosodimethylamine was devoid of vasodilator activityin vivoand exerted only minimal effects on isolated arterial smooth muscle tone or on arterial guanylate cyclase activity. The present data demonstrate a relationship between guanylate cyclase activation and arterial smooth muscle relaxation and suggest that the vasodilator effects on resistance vesselsin vivoin response to selectedN-nitroso compounds may involve such a mechanism. Although the significance of the presently reported cardiovascular responses toN-nitroso compounds is uncertain,N-nitroso compounds may represent a previously unrecognized class of substances which can be formed in the body and which possess marked vasodilator activity. It is possible that this vasodilator activity may involve the relaxation of vascular smooth muscle through activation of guanylate cyclase.

ISSN:0008-4212    

DOI:10.1139/y82-009

出版商:NRC Research Press    

年代:1982

数据来源: NRC

摘要:

Macrophages took up 3-O-methyl-D-glucose rapidly by facilitated diffusion using the glucose carrier and slowly by carrier-independent diffusion. Phloretin inhibited carrier-dependent but not carrier-independent diffusion. Estimates of intracellular water space based on 3-O-methyl-D-glucose uptake varied between 0.7 and 6.9 μL∙106cells−1for 2-week-old monolayer

ISSN:0008-4212    

DOI:10.1139/y82-010

出版商:NRC Research Press    

年代:1982

数据来源: NRC