摘要:

Erythromycin, an antibiotic used in the treatment of infectious diseases, produces gastrointestinal side effects such as diarrhea. The mechanisms by which erythromycin produces these effects are not known. However, erythromycin has been shown to increase gastrointestinal motor activity and to inhibit intestinal neutral amino acid absorption. Both effects could contribute to the gastrointestinal side effects observed. Because the intestinal systems of amino acid and sugar transport present similar characteristics, the aim of the present work was to determine whether erythromycin also altersD-galactose absorption and sucrase activity in rabbit jejunum. The results show that erythromycin diminishes intestinalD-galactose absorption. This effect seems to be due to an action mainly located on the Na+-dependent sugar transport of the mucosal border of the intestinal epithelium. Erythromycin also inhibits the Na+–K+ATPase activity of the enterocyte, which might explain the inhibition of theD-galactose Na+-dependent transport. However, a direct action of the erythromycin molecule on the Na+-dependent carrier cannot be excluded. Erythromycin did not alter sucrase activity.Key words: erythromycin, rabbit jejunum,D-galactose transport, sucrase activity.

ISSN:0008-4212    

DOI:10.1139/y93-029

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

Several studies have demonstrated that atrial natriuretic factor can bind to adrenal medulla cells. Furthermore, atrial natriuretic factor immunoreactivity has been identified in chromaffin cells. The aim of the present work was to investigate atrial natriuretic factor effects on the uptake, intracellular distribution, and release of norepinephrine in the rat adrenal medulla. Results showed that 100 nM atrial natriuretic factor induced a rapid increase of norepinephrine uptake during the first minute of the incubation period. This increase was maintained for up to 60 min. In addition, only neuronal norepinephrine uptake was increased by the natriuretic factor; non-neuronal norepinephrine uptake was unaltered. Atrial natriuretic factor modified the intracellular distribution of the amine store: the granular fraction of norepinephrine increased, while the cytosolic fraction decreased. On the other hand, different concentrations (10, 50, and 100 nM) of the atrial factor decreased spontaneous [3H]norepinephrine output in a concentration-dependent manner. Furthermore, atrial natriuretic factor (10 nM) also reduced high potassium solution evoked secretion of norepineprhine. These results suggest that atrial natriuretic factor modulates sympathetic activity in the rat adrenal medulla. These effects of atrial natriuretic factor may be related to the catecholamine peripheral mechanism involved in the regulation of arterial blood pressure, smooth muscle tone, metabolic activity, etc.Key words: adrenal medulla, atrial natriuretic factor, intracellular norepinephrine distribution, norepinephrine release, norepineprhine uptake.

ISSN:0008-4212    

DOI:10.1139/y93-030

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

The catabolism of intracerebroventricularly injected 5-hydroxytryptamine in mouse brain was investigated. Pretreatment of animals with the 5-hydroxytryptamine type 1 receptor antagonist metergoline, the 5-hydroxytryptamine type 2 receptor antagonist ketanserin, the 5-hydroxytryptamine reuptake inhibitor fluoxetine, or the selective 5-hydroxytryptamine neurotoxin 5,7-dihydroxytryptamine failed to alter the rate of catabolism of intracerebroventricularly administered 5-hydroxytryptamine. The monoamine oxidase inhibitor tranylcypromine effectively blocked degradation of injected 5-hydroxytryptamine and accumulation of 5-hydroxyindoleacetic acid. Coinjection of tryptamine with 5-hydroxytryptamine reduced the rate of conversion of 5-hydroxytryptamine to 5-hydroxyindoleacetic acid. These results indicate that intracerebroventricularly administered 5-hydroxytryptamine is removed by a monoamine oxidase dependent system. This catabolism is not affected by inhibition of presynaptic uptake, 5-hydroxytryptamine receptor type 1 or type 2 blockade, or destruction of serotonergic nerve terminals. The coadministration of tryptamine may prolong the residence period of 5-hydroxytryptamine through competition for monoamine oxidase.Key words: 5-hydroxytryptamine, tryptamine, monoamine oxidase, intracerebroventricular injection, catabolism.

ISSN:0008-4212    

DOI:10.1139/y93-031

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

Dietary zinc deficiency impairs desaturation and elongation of linoleic acid, but nothing is so far known about its effects on net whole-body utilization of linoleic or α-linolenic acids. By measuring intake, whole-body accumulation, and excretion of linoleic and α-linolenic acids, together with accumulation of their long-chain products, we hypothesized that a quantitative estimate could be obtained of their whole-body disappearance (apparent oxidation). This was evaluated in pregnant and nonpregnant rats given a low-zinc diet (3.4 vs. 34 mg zinc/kg diet in zinc-adequate controls). In the nonpregnant controls, low zinc intake did not significantly affect food intake or weight gain but did reduce whole-body accumulation of desaturated and (or) elongated products of linoleic and α-linolenic acids. In pregnant rats, low zinc intake reduced food intake and weight gain and doubled whole-body disappearance of linoleic and α-linolenic acids relative to that in the zinc-adequate controls. In contrast to the maternal fatty acid changes, low zonc intake had no significant effect on linoleic acid accumulation in the fetuses. We conclude that low zinc intake during pregnancy prevents the normal accumulation of long-chain fatty acids and differentially depletes maternal whole-body stores of linoleic and α-linolenic acids.Key words: fetus, linoleic acid, oxidation, pregnancy, zinc.

ISSN:0008-4212    

DOI:10.1139/y93-032

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

Dynorphin A-(1 – 13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia) was previously shown to be a highly potent and selective κ opioid peptide. Four analogs of Dyn Ia are synthesized by the solid-phase procedure, introducing pseudo CH2NH linkage between positions 6 and 7 as follows: analog 1, [6ψ7(CH2NH)]Dyn Ia; analog 2, [6ψ7(CH2NH),D-Leu8]Dyn Ia; analog 3, [N(Me)-Tyr1, 6ψ7(CH2NH)]Dyn Ia; and analog 4, [N(Me)-Tyr1,6ψ7(CH2NH),D-Leu8]Dyn Ia. The purified peptides are compared in vitro with Dyn Ia for their ability to compete with the binding of selective κ, μ, and δ opioid ligands using membrane preparations of guinea pig cerebellum (κ) and rat brain (μ and δ). The synthetic compounds are also compared in vivo in mice (intracerebroventricularly administered) for their analgesic activity against acetic acid induced writhing and their ability to produce motor dysfunction. All compounds display a high affinity (Ki = 0.5 – 1.8 nM) and a good selectivity for the κ opioid receptor, and their rank order of potency on the κ site (analog 2 > analog 1 > analog 3 > analog 4) closely parallels their potency (AD50 = 1.57–5 nmol/mouse) in inhibiting acetic acid induced writhing in mice (analog 2 > analog 1 > analog 4 > analog 3). On the other hand, all the synthetic analogs are less potent than Dyn Ia in producing motor effects, analog 2 being the least potent (CD50 = 15.4 nM as compared with 2.9 nM for Dyn Ia). Thus, analog 2 is a good model for developing Dyn A related peptides with selective antinociceptive activity.Key words: dynorphin, opioid receptors, analgesia, motor effects.

ISSN:0008-4212    

DOI:10.1139/y93-033

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [βAla8]NKA(4–10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [βAla8]NKA(4–10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists. SR 48968 (500 nmol/kg) was inactive against substance P as well as against the NK-2 or NK-3 selective agonists. RP 67580 (250 nmol/kg), CP-96,345 (250 nmol/kg), and SR 48968 (500 nmol/kg) per se did not induce any plasma extravasation, except in the urinary bladder, where CP-96,345 and SR 48968 increased EB concentrations in the tissue. These results suggest that the effects of neurokinins on vascular permeability vary from one tissue to another. The blockade of substance P by the NK-1 receptor selective antagonists, RP 67580 and CP-96,345, suggests that NK-1 receptors play an important role in the plasma extravasation induced by substance P. However, the effects of NK-2 and NK-3 receptor selective agonists appear to be independent of activation of NK-1 receptors since they are not blocked by RP 67580 or CP-96,345. Furthermore, because the effect of [βAla8]NKA(4–10), the NK-2 selective agonist, was not abolished by SR 48968, it is suggested that it might be mediated by the NK-2 receptor subtype NK-2B, which is less sensitive to SR 48968 than is NK-2A. The contribution of NK-3 receptors to plasma extravasation could not be adequately demonstrated in the present study because NK-3 antagonists sufficiently active in vivo are not available.Key words: neurokinins, RP 67580, CP-96,345, SR 48968, vascular permeability.

ISSN:0008-4212    

DOI:10.1139/y93-034

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

The osmosensitivity of peripheral vasopressin release was studied during healthy thermoregulation and endotoxin-induced fever. There was an increase in osmosensitivity following bolus injection of saline in febrile rats. These animals displayed a steeper slope in the linear relationship between plasma osmolality and plasma vasopressin levels compared with afebrile animals. The change in regression slope was due to a significantly lower plasma osmolality in febrile rats. The plasma osmolality of animals infused with hypertonic saline was similarly decreased, but data analysis failed to show a significant change in the regression slope. Osmotic thresholds were not altered in either group. There was an increased urine output in febrile rats, and consequently these animals excreted greater amounts of salts than afebrile rats. This could account for the lower plasma osmolality observed in the febrile rat.Key words: endotoxin, fever, osmolality, vasopressin.

ISSN:0008-4212    

DOI:10.1139/y93-035

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

Endothelin-1 (ET-1) is a 21 amino acid vasoconstrictor peptide produced by endothelial cells, the expression of which is modulated by a variety of vasoconstrictors, vasodilators, and inflammatory mediators. Hypoxia has been shown to increase ET-1 expression and release in cultured endothelial cells from the systemic circulation, but reports are contradictory regarding the pulmonary circulation. In this study, the release of ET-1 and its cellular localization in the isolated perfused newborn piglet lung were examined under control conditions and after stimulation with hypoxia or α-thrombin (positive control). In the control condition, perfusion pressure remained stable during the study period, and a progressive increase in levels of immunoreactive ET-1 (irET-1) was noted. When α-thrombin was added to the perfusion fluid, a slow gradual increase in perfusion pressure was produced and the levels of irET-1 were significantly greater than those measured in the control preparations. Finally, hypoxia produced a significant increase in the perfusion pressure; however, the release of irET-1 did not differ significantly from the control, if anything, the net release across the lung was diminished. In all conditions, immunocytochemistry using antiserum to human–porcine ET-1 revealed the presence of high ET-1-like immunoreactivity in epithelial cells of bronchi, bronchioles, and terminal bronchioles. In addition, endothelial cells of large and medium-size pulmonary arteries were only moderately immunoreactive for ET-1. These findings indicate that the neonatal pig lung can produce and release ET-1, and that its release can be increased by certain stimuli like α-thrombin. On the other hand, acute hypoxia does not appear to be an important stimulus to ET-1 in the neonatal pulmonary circulation. Therefore, ET-1 is not likely to be involved in the hypoxic pulmonary vasoconstriction in the newborn piglet.Key words: neonatal pulmonary circulation, endothelium-derived constricting factor.

ISSN:0008-4212    

DOI:10.1139/y93-036

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

The response to energy intake and expenditure is thought to be influenced by the genetic background. In the present study the metabolic response to pregnancy and to exercise training during pregnancy was investigated in two strains of rats. Lean Zucker and Wistar rats were divided into three groups: control pregnant (CP), exercise-trained pregnant (TRP), and not trained and not pregnant control (CNP). Trained rats swam 3 h per day, 6 days per week, throughout pregnancy. Body weight and food intake increased similarly during pregnancy in both strains (p ≤ 0.05). However, only Wistar rats had a further increase of food intake and body weight during the second half of pregnancy: TRP weighed 29.1 more grams and ate 4.5 more grams of food per day than CP at the end of pregnancy (p ≤ 0.05). Inguinal and parametrial fat cell sizes were unchanged during pregnancy. In both strains training induced a decrease of inguinal fat cell size at the beginning of pregnancy (p ≤ 0.05), which was rapidly counteracted to reach CP values on day 20 of pregnancy. Parametrial fat cell size was also decreased by training (p ≤ 0.05), but no values returned to control levels during pregnancy. In both strains, pregnancy increased fat cell lipolysis in the inguinal depot only (p ≤ 0.05). Training during pregnancy inhibited fat cell lipolysis in inguinal and parametrial depots, especially in Zucker (p ≤ 0.05), TRP reaching values similar to control values on day 20 of pregnancy. These results suggest that the effects of exercise training on the morphology of adipose tissue are similar in different strains of rats. They also show that the mobilization of fatty acids during pregnancy could respond to training in a strain-specific manner.Key words: adipose tissue, lipolysis, rat strain differences, pregnancy.

ISSN:0008-4212    

DOI:10.1139/y93-037

出版商:NRC Research Press    

年代:1993

数据来源: NRC

摘要:

The influence of repeated sampling by the biopsy technique on skeletal muscle's metabolic and force-output responses was studied using the in situ canine gastrocnemius preparation. The left muscle was stimulated (8 V, 0.2 ms) for 1 h at 3 Hz. In the biopsy series (n = 9) muscle samples were taken at rest, and at 0.5, 2, 5, 15, 30, 45, and 60 min of stimulation. In the control series (n = 8) the left and right muscles were quick-frozen in N2immediately after the 60 min of stimulation. The two series were not different in blood flow,, arterial or venous [H+], muscle glycogen, or lactate release throughout the 60 min of activity. The lactate release was transient and was associated with an accumulation of intramuscular lactate and a period of rapid glycogenolysis. The biopsy series had a modest but significantly (p < 0.05) higher muscle lactate concentration both at rest and at the end of the contractions. The biopsy series also had less (p < 0.05) tension development throughout the hour; however, the O2cost per unit of tension development was not different between groups, nor was the rate of tension decline over time different. This together with the similarities in perfusion, carbohydrate use, and lactate metabolism suggests that repeated biopsies had minimal impact on the muscle. The technique allows the collection of data over time; this improves the detail of experiments and means that fewer animals are required for a study.Key words: glycolysis, lactate, hydrogen ion, fatigue, muscle glycogen.

ISSN:0008-4212    

DOI:10.1139/y93-038

出版商:NRC Research Press    

年代:1993

数据来源: NRC