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Biomedical subjects

F Marques

Publications and source records attributed to F Marques.

At least 19 recordsLinked to original sources
PubMed2006

The choroid plexus response to peripheral inflammatory stimulus.

Increased interest is being raised on the interaction between systemic inflammation and the brain. The choroid plexus (CP) constitutes a monolayer of epithelial cells located within the brain ventricles and is responsible for the production of cerebrospinal fluid (CSF). Despite the knowledge that the CP capillaries are fenestrated, allowing free passage of molecules and cells, the involvement of the vast blood-brain boundary represented by the CP/CSF barrier in brain inflammatory processes has seldom been considered. In the present study we investigate, in mice, how the expression of genes encoding major constitutively expressed CP proteins is influenced by a systemic inflammatory stimulus. Confirming that the CP responds to peripheral inflammation, the messenger RNA (mRNA) levels of the pro-inflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha are rapidly induced. As for the constitutively expressed proteins, while the mRNA for genes encoding transthyretin and transferrin remain unaltered by the inflammatory challenge, that for prostaglandin D2 synthase (LPTGDS) is up-regulated at 6 h, and stays up-regulated up to 24 h after lipopolysacharide administration. Accordingly, LPTGDS CSF levels are also augmented. LPTGDS catalyzes the synthesis of the major prostanoid of the CNS and, being increased in the CSF, might mediate immune signaling into the brain. These observations emphasize that the CP must be considered a relevant mediator of immune signals between the periphery and the brain.

Animals↗
PubMed2005

Side effects in sea bass (Dicentrarchus labrax L.) due to intraperitoneal vaccination against vibriosis and pasteurellosis.

Sea bass (Dicentrarchus labrax L.) were injected intraperitoneally with monovalent (Photobacterium damselae subsp. piscicida or Vibrio anguillarum) and divalent (Ph. damselae subsp. piscicida and V. anguillarum) vaccine formulations, with or without adjuvants (mineral oil, liposome or alginate), to evaluate the short and long-term pathological effects. Eight animals from each group were sampled one, two, four and 11 months after intraperitoneal injection. The acute peritoneal response and the progression to a chronic status were evaluated by analysing peritoneal leucocytes collected during the first days post-injection. To evaluate the chronic response, the late peritoneal leucocyte response was analysed and the peritoneal cavity was examined and the intra-abdominal lesion level scored based on a pre-defined scale. Correlation between leucocyte exudative response, tissue inflammatory response and the development of granuloma were sought. The acute leucocyte response was characterized by an early (24-48 h) mobilization of neutrophils and macrophages, with phagocyte numbers dependent on the formulation, but no significant variations were observed in lymphocytes/small cells and EGCs. Later on, a steady increase occurred in lymphocytes/small cells and EGCs and a high concentration in neutrophils and macrophages was maintained up to 30-60 days in groups i.p. injected with oil adjuvanted formulations with antigen. All the lesions observed were moderate, indicating that in sea bass, the pathological effects due to intraperitoneally injected vaccines are less severe than in other fish species. The divalent oil adjuvanted vaccine induced the most severe side effects, with macroscopic granulomas consistently present up to 11 months.

Adjuvants, Immunologic↗
PubMed2005

Acute and chronic exposition of mice to severe hypoxia: the role of acclimatization against skeletal muscle oxidative stress.

The role of acclimatization and the effect of persistent severe hypoxia (7000 m) were analyzed in mice soleus muscle with respect to oxidative stress (glutathione redox status) and damage markers (TBARS and SH protein groups), NAG and SOD activities and HSP70 expression. Forty mice were divided into one normobaric-normoxic control group and four hypobaric-hypoxic experimental groups (n = 8). One experimental group (1 D) was acutely exposed to a simulated altitude of 7000 m in a hypobaric chamber for 1 day. Another experimental group (ACCL + 1 D) was exposed to a 3 days acclimatization period plus 1 day of hypoxia exposure at 7000 m. The third experimental group (ACCL + 8 D) was exposed to the same acclimatization protocol, remaining 8 subsequent days at 7000 m. The fourth experimental group (8 D) was chronically exposed without acclimatization. ACCL + 1 D showed a significant decrease (p < 0.05) in oxidative stress and damage compared to the 1 D group. Concerning chronic severe hypoxia, acclimatization was truly vital, since 8 D animals died after 5 days of exposure. Oxidative stress and damage markers in ACCL + 8 D tended to gradually increase throughout the 8 days of the hypoxic period. Total SOD activity did not change in 1 D compared to control; however, it increased significantly (p < 0.05) in ACCL + 1 D and ACCL + 8 D. HSP70 expression followed the observed oxidative stress and damage pattern, suggesting a protective role against hypoxia-induced oxidative stress. The present study supports the hypothesis that acclimatization attenuates oxidative stress and damage induced by acute hypoxia, although a trend to a gradually increased oxidative deleterious effect in skeletal muscle seems to occur during persistent severe hypoxia even after a previous acclimatization period.

Adaptation, Physiological↗
PubMed2003

Tangent double Hopf bifurcation in a differentially rotating cylinder flow.

A tangent double Hopf bifurcation has been found in a rotating cylinder flow driven by the counter-rotation of the top endwall. The codimension-3 tangent double Hopf point has been located using linear stability analysis. The nonlinear analysis of the multiple solutions in a neighborhood of this bifurcation point is performed by numerical solutions of the three-dimensional Navier-Stokes equations. At the tangent double Hopf point, two rotating waves and an unstable modulated rotating wave bifurcate simultaneously. A center manifold/normal form analysis is also performed, which is in very good agreement with both the linear and nonlinear computations. By a detailed exploration of the nonlinear flow, we have unraveled the complex dynamics generated by the mode competition, which is organized by the codimension-3 tangent double Hopf bifurcation.

Journal Article↗
PubMed2000

Dynamics of three-tori in a periodically forced navier-stokes flow

Three-tori solutions of the Navier-Stokes equations and their dynamics are elucidated by use of a global Poincare map. The flow is contained in a finite annular gap between two concentric cylinders, driven by the steady rotation and axial harmonic oscillations of the inner cylinder. The three-tori solutions undergo global bifurcations, including a new gluing bifurcation, associated with homoclinic and heteroclinic connections to unstable solutions (two-tori). These unstable two-tori act as organizing centers for the three-tori dynamics. A discrete space-time symmetry influences the dynamics.

Journal Article↗
PubMed2000

Insulin and high glucose modulation of phosphatase and reductase enzymes in the human erythrocytes: a comparative analysis in normal and diabetic states.

The ability of insulin to influence activities of various protein kinases and protein phosphatases, that are thought to mediate insulin action, are limited in patients with insulin resistance. Because numerous responses to insulin are affected, we undertook studies to determine whether protein tyrosine phosphatases (PTPs) activities are altered in patients with diabetes syndrome. In order to evaluate abnormal PTP activities, we done a comparative study using erythrocytes from normal and diabetic patients. We determined the activity of the cytosolic acid PTP in basal and insulin-dependent states. Mean basal PTP activities, were found to be significantly higher in diabetics than in normal subjects (type 1 diabetics: 0.36 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g hemoglobin (Hb), P < 0.001; type 2 diabetics: 0.35 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g Hb, P < 0.001). Insulin, at concentrations above physiological levels (1 mIU/ml), inhibited the PTP activities in erythrocytes from normal subjects (-15 +/- 4.1%, P < 0.01). Insulin could also modulate glycolysis, probably as a consequence of receptor tyrosine kinase activation, inducing phosphorylation of protein band 3 and hence the release of glycolytic enzymes. We have previously reported that a reductase enzyme in human erythrocytes is dependent on glycolysis being significantly activated (+28 +/- 3.1%, P < 0.001) by high insulin levels (1 mIU/ml). Mean basal reductase activities were found to be significantly lower in diabetics than in normal subjects (type 1 diabetics: 0.77 +/- 0.03 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001; type 2 diabetics: 0.77 +/- 0.04 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001), indicating altered erythrocyte metabolism in the diabetic patients. High glucose levels were used to mimic hyperglycemia condition, using erythrocytes from normal subjects. At 30 mM glucose, erythrocytic phosphatase activity was stimulated (+32 +/- 4.2%, P < 0.0001), although no effect was observed on the reductase enzyme at the same glucose levels. Results indicated that diabetic disorders appear to be associated with quantitative alterations of erythrocyte acid phosphatase activity and other enzymes that depend on the glycolytic rate (reductase). The overall data suggest that erythrocyte acid phosphatase may have a role in the modulation of glycolytic rates through the control of insulin receptor phosphorylation.

Acid Phosphatase↗
PubMed1999

Paroncomegas araya (Woodland, 1934) n. gen. et comb. (Cestoda: Trypanorhyncha: Eutetrarhynchidae) from the freshwater stingray Potamotrygon motoro in South America.

The trypanorhynch cestode originally designated Tentacularia araya is redescribed from its type host, Potamotrygon motoro (Potamotrygonidae), from specimens recently collected in Argentina and type material. The armature combines features of Eutetrarhynchus, Oncomegas, and Dollfusiella, indicating that its current placement in Eutetrarhynchus is incorrect and that the species represents a new genus. Paroncomegas n. gen. is proposed within the Eutetrarhynchidae Guiart, 1927, to accommodate Tentacularia araya as Paroncomegas araya n. comb. Eutetrarhynchus differs from Paroncomegas in the absence of a basal armature and basal swelling on the tentacles, from Dollfusiella by lacking macrohooks associated with the basal armature, and from Oncomegas, which possesses an asymmetrical basal swelling on the internal face of the tentaclc and a single macrohook on the external face of the basal armature. Paroncomegas is unique among these genera in possessing a chainette in the basal armature. All other genera currently recognized within the Eutetrarhynchidae can be distinguished from Paroncomegas by a distinct spatial divergence of hooks files 1(1'), resulting in a prominent space in views of the internal face. Two different morphotypes of P. araya can be distinguished in the material from Argentina, both infecting the same individual host specimens. They differ in the number and size of mature and gravid segments. Other characters concerning the tentacle armature, scolex features, and reproductive anatomy remain comparable.

Animals↗
PubMed1999

Scyphophyllidium uruguayense n. sp. (Eucestoda: Tetraphyllidea) in Mustelus mento (Cope, 1877) (Chondrichthyes: Carcharhiniformes: Triakidae) from La Paloma, Uruguay.

A new species of Scyphophyllidium inhabits Mustelus mento near La Paloma, Uruguay. It resembles Scyphophyllidium giganteum from the Atlantic Ocean and specimens identified as S. giganteum from California by having anapolytic strobilae 155-258 mm long, 250-300 craspedote proglottids, scoleces 1.2-1.4 mm wide, necks 34-41 mm long, immature and mature proglottids wider than long, gravid proglottids wider than long to longer than wide, genital pores averaging 28% of proglottid length from the anterior end, relatively flat ovaries with digitiform lobes reaching the lateralmost extent of the testicular field, vitellaria in 2 fields converging toward the proglottid midline, straight and short cirrus sacs, and postvaginal vas deferens. The bothridia of the new species have accessory bothridial suckers that are smaller than those of California specimens; European specimens reportedly lack accessory bothridial suckers. The new species possesses a uterine duct that joins the uterus at the level of the genital atrium and ventral osmoregulatory ducts medial rather than lateral to the dorsal ducts, an arrangement described for Californian but not European specimens. It differs from both European and Californian specimens by having longer cirri, more testes per proglottid, prominent scales covering the neck, and vaginae and uterine ducts coiled immediately preovarially. Pithophorus, Marsupiobothrium, and Scyphophyllidium may form a clade.

Animals↗
PubMed1998

Cdk2 activity is dispensable for the onset of DNA replication during the first mitotic cycles of the sea urchin early embryo.

Earlier work reported the important role of Cdk2 as a regulator of DNA replication in somatic cells and in Xenopus extracts. In the present report we analyze in vivo the involvement of Cdk2 in DNA replication during early embryogenesis using the first mitotic cycles of sea urchin embryos. Unfertilized Sphaerechinus granularis eggs are arrested after the second meiotic cytokinesis. Fertilization resumes the block and induces DNA replication after a short lag period, making sea urchin early embryo a good model for studying in vivo the onset of DNA replication. We show that Cdk2 as well as its potential partner cyclin A are present in the nucleus in G1 and S phase and therefore available for DNA replication. In accordance with data obtained in Xenopus egg extracts we observed that Cdk2 kinase activity is low and stable during the entire cycle. However, in contrast with this in vitro system in which Cdk2 activity is required for the onset of DNA replication, the specific inhibition of Cdk2 kinase by microinjection of the catalytically inactive Cdk2-K33R or the inhibitor p21(Cip1) does not prevent DNA replication. Because olomoucine, DMAP, and emetine treatments did not preclude DNA synthesis, neither cyclin A/Cdk1 nor cyclin B/Cdk1 kinase activities are necessary to replace the absence of Cdk2 kinase in promoting DNA replication. These data suggest that during early embryogenesis Cdks activities, in particular Cdk2, are dispensable in vivo for the initiation step of DNA replication. However, the specific localization of Cdk2 in the nucleus from the beginning of M phase to the end of S phase suggests its involvement in other mechanisms regulating DNA replication such as inhibition of DNA re-replication and/or that its regulating role is achieved through a pathway independent of the kinase activity. We further demonstrate that even after inhibition of Cdk activities, the permeabilization of the nuclear membrane is required to allow a second round of DNA replication. However, in contrast to Xenopus egg extracts, re-replication can take place in the absence of DMAP-sensitive kinase.

Adenine↗
PubMed1997

Koronacantha pectinaria n. comb. (Acanthocephala: Illiosentidae) from Microlepidotus brevipinnis (Haemulidae) and redescription of Tegorhynchus brevis.

Tegorhynchus pectinarius Van Cleave, 1940, is redescribed on the basis of male and female specimens in Microlepidotus brevipinnis from the marine waters of Costa Rica and México. The elongate proboscis with a heavy cuticular coating, cuticular body spines, 8 cement glands, and the heavy, strongly recurved hooks in the shape of an inverted apostrophe with roots that are simple but exaggerated in size with a small hook blade indicate that T. pectinarius should be assigned to Koronacantha Monks and Pérez-Ponce de León, 1996. Koronacantha pectinaria n. comb. can be distinguished from Koronacantha mexicana in having strongly recurved hooks only on the dorsal side of the proboscis, a conspicuous patch devoid of normally developed hooks located just anterior to the recurved hooks, trunk spines extending from the anterior end of the trunk posteriorly over 85% of the trunk, lacking genital spines in both sexes, and by the basal comblike group of small close-set hooks made up of 5 to 7 hooks. In K. mexicana, the recurved hooks occur as a complete ring, no patchlike area devoid of hooks exists, trunk spines begin at posterior end of receptacle and extend posteriorly over rest of trunk, genital spines are present in both sexes, and the basal comblike group of small close-set hooks consists of 4 or 5 hooks. Tegorhynchus brevis Van Cleave, 1921, is redescribed based on the original specimens, and Tegorhynchus, Koronacantha, and Illiosentis are considered diagnostically distinct.

Acanthocephala↗
PubMed1997

Two new species of Acanthobothrium in Narcine entemedor (Rajiformes: Narcinidae) from the northwest coast of Guanacaste Peninsula, Costa Rica.

This paper describes 2 new species of Acanthobothrium collected in Narcine entemedor from Cuajiniquil, Guanacaste Province, Costa Rica (10 degrees 57'N, 85 degrees 42'W). Acanthobothrium franus n. sp. averages 27 mm long, composed of 110 proglottides, has bothridial hooks 344-469 microns long, and 24-56 testes per proglottis. This new species resembles Acanthobothrium colombianum, Acanthobothrium coquimbensis. Acanthobothrium dujardini, Acanthobothrium lineatum, Acanthobothrium lintoni, and Acanthobothrium paulum. The new species differs from these 6 species by having a relatively shorter cirrus sac length not reaching the middle region of the proglottis. Additionally, A. franus differs from these species by having longer bothridia (627-1,408 microns vs. 299-391 microns for A. colombianum, 312-480 microns for A. coquimbensis, 240-560 microns for A. dujardini, 275-624 microns for A. lineatum, 389-720 microns for A. lintoni, and 300-880 microns for A. paulum), and larger bothridial hooks (344-469 microns vs. 175-193 microns, 120-192 microns, 180-210 microns, 118-216 microns, 108-230 microns, and 104-229 microns, respectively). Acanthobothrium inbiorium n. sp. averages 59 mm long, composed of 198 proglottides, has bothridial hooks 95-120 microns long, and possesses 44-73 testes per proglottis. Among species of Acanthobothrium, the new species resembles Acanthobothrium electricolum, Acanthobothrium dasybati, Acanthobothrium dighaensis, Acanthobothrium icelandicum, Acanthobothrium indicum, Acanthobothrium microcephalum, and Acanthobothrium wedli. The new species closely, resembles A. dasybati, but differs from that species in average strobila length and number of proglottides (58 microns long and 198 proglottides in A. inbiorium vs. 20 and 80 in A. dasybati, respectively). The new species can be distinguished from A. electricolum by having a wider scolex (450-900 microns vs. 189-252 microns), from A. dighaensis by having a narrower scolex (450-900 vs. 1,050-1,429), and from A. indicum by average strobilar length and number of proglottides (58 mm and 198 for A. inbiorium vs. 25 mm and 145 for A. indicum). Finally, A. inbiorium differs from A. icelandicum by having a shorter cirrus sac (122-285 for A. inbiorium vs. 380-410 for A. icelandicum), and A. microcephalum and A. wedli by having longer bothridia (an average of 603 microns vs. 447 microns for A. microcephalum and 350 microns for A. wedli), and fewer testes per proglottis (44-73 vs. 105-115 and 80-100, respectively). Morphological similarities suggest that some components of the eastern Pacific fauna of Acanthobothrium might share historical associations with the Caribbean and the western Pacific/Indian Ocean fauna.

Animals↗
PubMed1997

[Value of a predictive model of ambulatory blood pressure integrating physical activity].

OBJECTIVE: To determine how much of the variations of blood pressure during a 24 hour period could be accounted for by a change in activity and establish a predictive model. MATERIALS AND METHODS: Twenty three healthy subjects (mean age 25 +/- 2 years) were studied. The BP, heart rate (HR), and time of measure (T) were recorded by ambulatory BP monitoring using Spacelabs (4 measures per hour). At each measure the subject noted in a diary the degree of activity on a six level semi-quantitative scale. DATA ANALYSIS: A model was constructed using an analysis of covariance. Different parameters were added in succession to reach a model of the type P: P0 + A + beta + (HR-HR0) + H, were P = predicted systolic pressure, P0 = mean systolic BP over the 24 hours. A variation in systolic BP for activity level, beta = the slope of the regression between systolic BP and HR during activity A, and HR0 the mean HR during this activity. RESULTS: 1) In order to test the model, the values measured in one subject were compared to the predicted values from the model in 22 others. The procedure was then repeated for the other subjects. This common model predicted 41 +/- 21% of fluctuations in BP of the subject analysed with a range of 0 to 66%. 2) In order to refine the individual model two subjects were explored 7 times over 24 h of non consecutive days. The measures of the last recording were compared to the predicted values from the application of the model to the six preceding recordings. The model then predicted 81% and 66% of the BP values of the test day. The mean of the 24 hour individual difference over a one hour period between the measures and its predicted value by the model was 0.13 +/- 4.8 mmHg, and -0.75 +/- 7.7 mmHg. CONCLUSION: This study expresses in a quantitative fashion the importance of the level of activity in the evaluation of the level of ambulatory BP. The introduction of this method of quantification and analysis seems logical in therapeutic trial. The difference in the predictions by the model for some subjects poses the problem of uniform coding of activities and that of the recognition of other events such as stress and dreaming in sleep.

Adult↗
PubMed1996

Two new species of tetraphyllidean cestodes in Himantura pacifica (Chondrichthyes: Myliobatiformes: Dasyatididae) from the northwest coast of Costa Rica.

Two new species of tetraphyllidean cestodes inhabiting Himantura pacifica from the northwest coast of Costa Rica are apparently most closely related to species inhabiting Himantura schmardae from the Atlantic coast of Colombia. Acanthobothroides pacificus n. sp. differs from Acanthobothroides thorsoni, the only other species in the genus, primarily by having smaller lateral (98-123 microns rather than 168-198 microns long) and medial (handles 92-116 microns rather than 162-168 microns long) hooks, and more testes (up to 125 rather than up to 97) per proglottis. The generic diagnosis of Acanthobothroides is modified to include the presence of a small inner prong on the large medial bothridial hooks. Rhinebothrium geminum n. sp. and Rhinebothrium magniphallum are the only 2 species in the genus possessing unusually long cirrus sacs, extending from the genital atrium all the way to the ovarian isthmus; R. geminum averages 12 (12-14) loculi per bothridium and 11 (9-12) testes, whereas R. magniphallum averages 17 (16-18) loculi and 14 (10-16) testes per proglottis.

Animals↗
PubMed1995

Five new species of Acanthobothrium van Beneden, 1849 (Eucestoda: Tetraphyllidea: Onchobothriidae) in stingrays from 1he Gulf of Nicoya, Costa Rica.

Five new species of Acanthobothrium are described in stingrays from the Gulf of Nicoya, Costa Rica. Acanthobothrium costarricense n. sp. in Dasyatis longus, most similar to Acanthobothrium lilium, Acanthobothrium lineatum, and Acanthobothrium himanturi, has bothridial hooks averaging 125 microns (lateral) and 145 microns (medial) long, an average of 47 testes per proglottis, cirrus sacs averaging 187 microns long, and asymmetrical ovarian lobes with poral lobes reaching the posterior margin of the cirrus sac, and aporal lobes reaching the middle of the cirrus sac. Acanthobothrium cimari n. sp. in D. longus, most similar to A. lilium, A. lineatum, A. himanturi, A. costarricense, and Acanthobothrium semnovesiculum, has bothridial hooks averaging 117 microns (lateral) and 121 microns (medial) long, an average of 50 testes per proglottis, cirrus sacs averaging 164 microns long, and asymmetrical ovarian lobes with poral lobes reaching the posterior margin of the cirrus sac, and aporal lobes reaching the level of the vagina. Acanthobothrium puntarenasense n. sp. in D. longus, distinctive in having a very small scolex relative to the width of the cephalic peduncle similar to Acanthobothrium microcephalum, has bothridial hooks averaging 111 microns (lateral) and 117 microns (medial) long, an average of 50 testes per proglottis, cirrus sacs averaging 170 microns long, and asymmetrical ovarian lobes with poral lobes reaching the posterior margin of the cirrus sac, and aporal lobes reaching the middle of the cirrus sac. Acanthobothrium vargosi in D. longus, most similar to Acanthobothrium brevissime, Acanthobothrium tasajerasi, Acanthobothrium urotrygoni, and Acanthobothrium campbelli, has bothridial hooks averaging 130 microns (lateral) and 133 microns (medial) long, an average of 25 testes per proglottis arranged in 2 single rows, cirrus sacs averaging 91 microns long, and asymmetrical ovarian lobes with poral lobes reaching the posterior margin of the cirrus sac, and aporal lobes reaching the middle of the cirrus sac. Acanthobothrium campbelli n. sp. in Urotrygon chilensis, most similar to a A. brevissime, A. Vargasi, A. lineatum, A. himanturi, and A. urotrygoni, has bothridial hooks averaging 108 microns (lateral) and 111 microns (medial) long, an average of 19 tester per proglottis arranged in 2 nearly linear rows, cirrus sacs averaging 74 microns long, and asymmetrical ovarian lobes with the poral lobe reaching the posterior margin of the cirrus sac, and the aporal lobes reaching the middle of the cirrus sac.

Animals↗
PubMed1988

Lung function in the workers of a cromate producing industry.

Lung function and radiographic study was realized on 184 workers in a chromate producing industry (113 chronically exposed, 41 intermittently exposed and 30 unexposed). Prevalences were 22 (11.9%) cases of obstructive ventilatory pattern, 22 (11.9%) restrictive and 18 (9.7%) mixed. In the different ventilatory disfunction patterns, multivariant analysis in the three exposure groups, controlled by the tobacco variable, was statistically significant between exposure and restrictive ventilatory pattern (p = 0.0065). None of the workers presented radiologic alterations according to the ILO, 1980.

Adult↗
PubMedDate not supplied

Activation of a NADH dehydrogenase in the human erythrocyte by beta-adrenergic agonists: possible involvement of a G protein in enzyme activation.

NADH dehydrogenase in the plasma membrane transfers electrons from NADH to external oxidants like ferricyanide, through pathways which are linked to metabolic processes in the cell. Hormone binding to specific sites (receptors) can modify the enzyme activity, suggesting a direct or indirect coupling between the redox system and the hormone receptors. Reduction of external ferricyanide to ferrocyanide by human erythrocytes was stimulated by beta-adrenergic agonists (adrenaline, ritodrine and isoxsuprine), this effect being dependent upon concentration and pH. The agonist-stimulatory effect was attenuated in the presence of metoprolol (10(-4) M), a beta-adrenergic antagonist, and was not modified in the presence of prazosin, an alpha-adrenergic antagonist, suggesting that modification of the redox activity is mediated by binding of the agonists to beta-adrenergic receptors present in the human erythrocytes. Basal and agonist-dependent activities were inhibited in the presence of sulfhydryl reagents p-chloromercuribenzoate (PCMB, 10(-5) M) and N-ethylmaleimide (NEM, 10(-3) M), indicating the involvement of -SH groups. Inactivation by NEM was reversed by washing the cells with GTP (10(-3) M) and GTP gamma S (10(-4) M), suggesting that the specific alkylated -SH group(s) is located on a G protein in the hormone-receptor-G-protein complex. The human erythrocytes contain G proteins, displaying both guanine-nucleotide-binding properties and GTPase activity. Fluoride (10(-2) M) and fluoroaluminate (AlF4- (F-, 10(-2) M + Al3+, 10(-5) M), G protein activators, enhanced the basal and agonist-dependent activities, suggesting the involvement of G proteins in this system. The overall results indicated that one of the coupling components between the hormonal receptors and the redox system is probably a G protein, and the mechanism of enzyme activation after hormone binding to the receptor is based on the redox state of cysteine residues probably within the receptor-G-protein complex.

Adrenergic alpha-Antagonists↗