Biomedical subjects

V Martínez

Publications and source records attributed to V Martínez.

At least 19 recordsLinked to original sources

PubMed2006

Disturbance of erythrocyte lipid bilayer by amino acid-based surfactants.

In an attempt to increase our knowledge regarding the mechanisms of surfactant membrane interaction, we studied the action of several anionic and cationic amino acid-based surfactants on membrane fluidity using fluorescence anisotropy. Anisotropy measurements demonstrated that almost all of the surfactants studied disturbed the external region of the erythrocyte membrane without affecting the core of the bilayer. How the physico-chemical properties and structure of these compounds affect dynamics of the lipid bilayer is discussed in detail.

Amino Acids↗

PubMed2006

5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor function through 5-HT4 receptors in conscious mice.

Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility and secretion. We characterized the action of the 5-HT precursor 5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor activity in conscious mice. Fos immunoreactivity (IR), used as a marker of neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole mount preparations of the distal colon 90 min after an intraperitoneal injection of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a dose-related manner, with a peak response observed within the first 15 min postinjection. 5-HTP (0.5-10 mg/kg) dose dependently increased Fos expression in myenteric neurons, with a maximal response of 9.9 +/- 1.0 cells/ganglion [P < 0.05 vs. vehicle-treated mice (2.3 +/- 0.6 cells/ganglion)]. There was a positive correlation between Fos expression and fecal output. Of Fos-positive ganglionic cells, 40 +/- 4% were also pChAT positive and 21 +/- 5% were NADPH-diaphorase positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos expression were completely prevented by pretreatment with the selective 5-HT4 antagonist RS-39604. These results show that 5-HTP injected peripherally increases Fos expression in different populations of cholinergic and nitrergic myenteric neurons in the distal colon and stimulates propulsive colonic motor function through 5-HT4 receptors in conscious mice. These findings suggest an important role of activation of colonic myenteric neurons in the 5-HT4 receptor-mediated colonic propulsive motor response.

5-Hydroxytryptophan↗

PubMed2006

Salinity tolerance of 'Valencia' orange trees on rootstocks with contrasting salt tolerance is not improved by moderate shade.

The effects of shading in combination with salinity treatments were studied in citrus trees on two rootstocks with contrasting salt tolerance to determine if shading could reduce the negative effects of salinity stress. Well-nourished 2-year-old 'Valencia' orange trees grafted on Cleopatra mandarin (Cleo, relatively salt tolerant) or Carrizo citrange (Carr, relatively salt sensitive), were grown either under a 50% shade cloth or left unshaded in full sunlight. Half the trees received no salinity treatment and half were salinized with 50 mM Cl- during two 9 week salinity periods in the spring and autumn interrupted by an 11 week rainy period. The shade treatment reduced midday leaf temperature and leaf-to-air vapour pressure deficit regardless of salinity treatments. In non-salinized trees, shade increased midday CO2 assimilation rate (A(CO2)) and stomatal conductance, but had no effect on leaf transpiration (E(lf)). Shade also increased leaf chlorophyll and photosynthetic water use efficiency (A(CO2)/E(lf)) in leaves on both rootstocks and increased total plant dry weight in Cleo. The salinity treatment reduced leaf growth and leaf gas exchange parameters. Shade decreased Cl- concentrations in leaves of salinized Carr trees, but had no effect on leaf or root Cl- of trees on Cleo. There were no significant differences in leaf gas exchange parameters of shaded and unshaded salinized plants but the growth reduction from salinity stress was actually greater for shaded than for unshaded trees. Shaded trees on both rootstocks had higher leaf Na+ than unshaded trees after the first salinity period, and this shade-induced elevated leaf Na+ persisted after the second salinity period in trees on Carr. Thus, shading did not alleviate the negative effects of salinity on growth and Na+ accumulation.

Carbon Dioxide↗

PubMed2006

[Moyamoya disease: follow-up of 12 patients].

INTRODUCTION: We present 12 patients with moyamoya disease and their evolution from an early age to adulthood in some cases. MATERIAL AND METHODS: The patients (nine females and three males) were first studied before 10 years of age because of neurological disease. Bilateral carotid and vertebrobasilar arteriographies were performed during initial evaluation. In the patients who were followed-up during several or many years (in one, during 33 years and, in two, during 25 years), neuroimaging studies were done by magnetic resonance angiography (MRA). One patient also had neurofibromatosis type 1 (NF1). RESULTS: All patients showed bilateral occlusion of the supraclinoid portion of the internal carotid arteries. The basilar artery was markedly narrowed in one patient. One patient with very early onset of symptoms also showed collateral vascularization through the Bernasconi- Cassinari artery. Cerebral multifocal cortical and subcortical lesions were seen in the patients who had very long follow-up, although these already had appeared in the first MR studies. One patient showed arterial moyamoya 31 images and fibromuscular dysplasia. She was the only patient treated surgically during childhood with death after a short time. Another patient had a pregnancy and vaginal delivery at 26 years of age without complications. Images of moyamoya did not disappear in any of the patients in this series. Seizures were controlled with antiepileptic medication in all patients except in one who had NF1 and severe cerebral lesions. Although it is difficult to demonstrate the efficacy of calcium-antagonist medication (nicardipine), we found that it improved the neurological symptoms in most of our patients. CONCLUSIONS: Long-term follow-up of the patients in this series showed some neurological problems, although most of them did well, including those cases with early onset of symptoms. All adult patients in this series were working, although some of them in low qualified jobs. Collateral vascularization was very marked in all patients except in one who also showed fibromuscular dysplasia. Moyamoya images did not disappear in any patient. Ischemic cerebral lesions seem to be underlying the cause of the neurological sequelae. Seizures responded well to antiepileptic medication.

Child↗

PubMed2005

Smoking habit and genetic factors associated with lung cancer in a population highly exposed to arsenic.

In order to find some relationship between genetic differences in metabolic activation and detoxification of environmental carcinogens and host susceptibility to chemically induced cancers, we have investigated the distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung cancer patients and healthy volunteers of the second region in the north of Chile highly exposed to arsenic. The main sources of environmental arsenic exposure in Chile are copper smelting and drinking water, specially in the second region, the most important copper mining region in the world that shows the highest lung cancer mortality rate in the country (35/100.00). The population of Antofagasta, the main city of the region was exposed between 1958 and 1970 to arsenic concentrations in drinking water of 860 microg/m3, presently declining to 40 microg/m3. For men the MspI CYP1A1 *2A genotype was associated with a highly significant estimated relative lung cancer risk (O.R. = 2.60), but not GSTM1 by itself. The relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habits (O.R. = 2.98). In the second region the cancer mortality rate for As associated cancers, might be related at least part to differences in As biotransformation. In this work we demonstrate that genetic biomarkers such as CYP1A1 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with higher risk for lung cancer, due to arsenic exposure.

Adult↗

PubMed2005

Micronuclei assessment in buccal cells of people environmentally exposed to arsenic in northern Chile.

To determine the genotoxic risk associated to environmental arsenic exposure, the frequency of micronuclei in buccal cells (BCMN) of people drinking arsenic-contaminated water has been evaluated. A group of 105 individuals from the Antofagasta region (north Chile), and 102 individuals from the area of Concepcion, used as reference group, were included in the study. Arsenic concentration in drinking water was high (0.75 mg/L) in the Antofagasta area, 75-fold the maximum recommended level by WHO (0.01 mg/L), while the values obtained in Concepcion were significantly lower (0.002 mg/L). Individual measures of arsenic exposure were also determined in fingernails, which clearly confirm the existence of chronic exposure in the sampled populations from the Antofagasta region (10.15 microg/g versus 3.57 microg/g). The cytogenetic results indicate that, although the BCMN frequency is higher in exposed than in controls, this increase does not attain statistical significance. When the exposure biomarkers were related with the cytogenetic values, no correlations were observed between BCMN and arsenic content in water or in fingernails. In addition, the genotoxicity values do not seem to be related to the ethnic origin from people belonging to the exposed group. As a conclusion it appears that, in the studied population, the chronic ingestion of arsenic-contaminated water does not induce cytogenetic damage, measured as micronuclei, in the cells of the oral mucous in a significant extent.

Adult↗

PubMed2005

[Cochlear involvement in acute otitis media].

OBJECTIVE: An experimental design with mice has been realized to understand the origin of sensorial hearing loss related to infectious processes in the middle ear. Our aim is to study if the cilliated cells in the Corti organ's are lost after one or more acute otitis media. MATERIAL AND METHODS: For that, thirty Sprague-Dawley mice have been divided in two groups. In the first one, we have induced one acute otitis media, in the second group we have induced two infections of this kind. RESULTS: The statistic study shows that the loss of the cilliated cells is greater in the basal turn of the mice is cochlea, in the first group (alpha=0,020) and also in the second (alpha=0,038). We've noticed in the first group the near absence of injury in the middle turn, but in all samples of the second group we found that injury (alpha=0,002). CONCLUSIONS: In acute otitis media, the loss of ciIliated cells are mainly in the basal turn of the mice is cochlea, and affects the middle turn when the infection is repeated.

Acute Disease↗

PubMed2005

CYP1A1 and GSTM1 genetic polymorphisms in lung cancer populations exposed to arsenic in drinking water.

Region II of Chile is the most important copper mining area in the world and it shows the highest lung cancer mortality rate in the country (35/100,000). The population in Antofagasta, the main city of Region II, was exposed from 1958 to 1970 to 860 microg m(-3) arsenic (As) in drinking water and has currently been declining to 40 microg m(-3). Glutathione serves as a reducing agent and glutathione S-transferase (GST) may have an important role in As methylation capacity and body retention. In the current study, the null genotype of GSTM1 and the MspI polymorphism of CYP450 1A1 were investigated in lung cancer patients and in healthy volunteers of Region II. In males, the 2A genotype of MspI represented a highly significant estimated relative lung cancer risk (OR=2.60). Relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habit (OR=2.98). In Region II, the cancer mortality rate for As-associated cancers at least partly might be related to differences in As biotransformation. Genetic biomarkers such as 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with a high risk for lung cancer as prevention and protection actions to protect public health.

Arsenic↗

PubMed2005

Interaction between surgical procedure for repairing retinal detachment and clinical risk factors for proliferative vitreoretinopathy.

PURPOSE: To asses risk factors of proliferative vitreoretinopathy (PVR) and a model for predicting it. METHODS: Observational, case-control. 335 patients with non-complicated retinal detachment (RD) were included: 134 developed PVR (Cases); 201 patients did not (Controls). Risk factors for PVR were identified by multivariate analysis. Influence of variables was assayed according to the surgical approach. By logistic regression analysis a model to predict the risk of developing PVR and odds ratio (OR) values for each clinical factor were estimated. RESULTS: Risk was higher in patients > 70 years and with intraocular pressure lower than 14 (OR: 3.84; CI 95%: 2.04-7.30) and in retinal breaks larger than "1 clock hour" (OR: 2.54; CI: 1.28-5.05), extended retinal detachments (OR: 4.01; CI: 1.98-8.10) and reinterventions (OR: 1.55; CI: 1.14-9.22). Scleral surgery also was a risk factor (OR: 3.89; CI: 2.12-7.14) and aphakia/pseudophakia when scleral surgery is performed (OR: 3.33; CI: 1.54-7.22). A model to predict PVR was proposed with these results. CONCLUSIONS: Surgical approach modifies risk factors of PVR, and should be taken into account to improve the models for predicting it.

Adolescent↗

PubMed2004

Evaluation of micronucleus induction in a Chilean population environmentally exposed to arsenic.

In the present study we have evaluated whether or not environmental exposure to arsenic in ground drinking-water results in a significant increase in the frequency of micronuclei (MN) in peripheral blood lymphocytes. Thus, 106 individuals from the Antofagasta region (North Chile), together with 111 individuals from the area of Concepción, were used in this investigation. In the Antofagasta area, arsenic levels in drinking-water as high as 0.750 mg/L were measured. In Concepción, located about 2500 km towards the south and used as reference area, arsenic levels in tap water were as low as 0.002 mg/L. The total content of arsenic in fingernails was determined as a biomarker of individual exposure. The cytogenetic results obtained in this study indicate that in the exposed group the overall frequency of binucleated micronucleated cells (BNMN) is higher than in the reference group, the difference being statistically significant. In addition, no differences were found between the exposed and the reference groups, regarding the cytokinesis-block proliferation index (CBPI). No association was observed between BNMN and arsenic content in water or arsenic in fingernails. On the other hand, when the exposed group was divided according to their Atacameno or Caucasian ethnicity, no significant differences were observed between them. In addition, as usually found in other human biomonitoring studies, sex and age are factors that modulate the frequency of MN in both exposed and reference populations.

Adult↗

PubMed2004

Assessment of primary eye and skin irritants by in vitro cytotoxicity and phototoxicity models: an in vitro approach of new arginine-based surfactant-induced irritation.

Extensive efforts have been made, recently, to find surfactants with lower irritation potential than those presently commercially available, for use in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of a novel family of dicationic arginine-diglyceride surfactant compounds, 1,2-diacyl,3-O-(l-arginyl)-rac-glycerol with alkyl chain lengths in the range from 8 to 14 carbon atoms, were compared to three commercial surfactants. The end-points used to assess toxicity were the red blood cell lysis assay and uptake of the vital dye neutral red 24h after dosing (NRU), respectively. Two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, were used as in vitro models to predict the potential phototoxicity which could result in irritation, determined by resazurin reduction to resorufin and neutral red uptake (NRU). All tested surfactants had cytotoxicity effects as demonstrated by and decrease of NR uptake, which showed a clear concentration-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC(50)) range from 1 microM(-1) (hexadecyl trimethyl ammonium bromide) to 565 microM(-1) (12,12-l-arginine). Erythrocyte haemolysis also showed a clear concentration-response relationship, the 50% of haemolysis ranged from 37 microM(-1) (10,10-l-arginine) to 151 microM(-1) (sodium lauryl sulphate). Phototoxicity was performed with 12,12-l-acetyl-arginine, the most stable chemical structure. The validated 3T3 NRU photoxicity assay was used and revealed a phototoxic potential.

Animal Testing Alternatives↗

PubMed2004

Capillary electrophoresis as a useful tool for the analysis of chemical tracers applied to hydrological systems.

A capillary electrophoretic method was optimised for the separation and determination of iodide used as artificial tracer in hydrology. The influence of the buffer concentration and pH, electroosmotic flow modifier concentration (cetyltrimethylammonium bromide (CTAB)), the injection time and voltage applied, on the electrophoretic separation was studied. A running buffer of 20 mM phosphate (pH 8) containing 1 mM CTAB was found to provide the optimum separation of iodide with respect to resolution, migration time and selectivity. The water samples were injected hydrostatically at 10 cm for 110 s, the voltage applied was -20 kV and a detection wavelength of 214 nm. The influence of the sulphite added to water samples in order to prevent the oxidation of iodide to iodate was also studied. This method can be applied to the determination of iodide free of sulphite interference up to at least a ratio of 1:1000 (I(-):SO3(2-)). The other inorganic anions, which are present in the water samples (mainly chloride, sulphate, nitrate, carbonate), do not interfere with the determination of iodide. This method allows the simultaneous determination of bromide, nitrite, and nitrate together with iodide. The electrophoretic method showed to be linear from 0.5 to 5 mg l(-1) of iodide (the migration time was 2.6 min) with a quantitation limit of 0.45 mg l(-1) and a intraday repeatability lower than 4% of R.S.D. at different concentration levels.

Electrophoresis, Capillary↗

PubMed2004

Nutritional status of indigenous children at boarding schools in northern Mexico.

OBJECTIVE: To assess the nutritional status of Tarahumara children at indigenous boarding schools. DESIGN: Cross-sectional comprehensive nutritional survey. SETTING: The schools sampled were located in indigenous municipalities of the northern Mexican state of Chihuahua. SUBJECTS: The study was carried out in 2001 among 331 children aged 6-14 y from a sample of five schools. Anthropometric measurements, a thyroid exam and capillary haemoglobin levels were obtained from the children. Serum concentrations of ferritin, iron, total iron-binding capacity, vitamin B(12), folic acid and zinc were collected from a subsample of 100 children. RESULTS: The prevalence of wasting and overweight (children 6-9 y) was 1.1 and 4.6%, respectively, and of underweight, risk of overweight and overweight (10-14 y) was 3.2, 5.1 and 0.6%, respectively. Stunting (6-12 y) was present in 22.3% of the children. The total goitre rate was 5.4%. The prevalence of anaemia was 13% (boys 11.4, girls 14.5%). Overall, 24.2% of the children were iron deficient (depletion 11.1%, deficient erythropoiesis 3%, iron deficiency anaemia 10.1%). No child had folic acid values <3 ng/ml, but 20.2% had low (<200 microg/dl) and 27.3% marginal (200-300 microg/dl) vitamin B(12) levels, and 80.2% had low zinc concentrations (<60 microg/dl). CONCLUSIONS: Nutritional underweight and stunting were similar to those reported in rural localities at the national level, but overweight was less prevalent in children aged 10-14 y. Various micronutrient deficiencies was identified including zinc and vitamin B(12), but the prevalence of iron and folic acid deficiency was lower than expected. These results suggest that Tarahumara children attending boarding schools may be the better-off children from these extremely poor and marginalized areas. SPONSORSHIP: Swedish Agency for Research Cooperation with Developing Countries and the Mexican Social Security Institute.

Adolescent↗

PubMed2003

Susceptibility and exposure biomarkers in people exposed to PAHs from diesel exhaust.

Xenobiotic metabolizing enzymes, especially CYP1A1 and GSTM1, are involved in the activation and conjugation of PAHs and are controlled by polymorphic genes. PAHs released from diesel emissions in many cities of the world, especially in developing countries, contribute significantly to the toxic effects of airborne inhalable particles. We have evaluated the gene-environment interaction in Santiago of Chile, studying the contribution of CYP1A1 and GSTM1 polymorphisms on 1-OH-P urinary levels used as the PAHs exposure biomarker. The study was performed on 59 diesel exposed (38 diesel revision workers and 21 subjects working in an urban area as established street vendors) and 44 non-exposed subjects living in a rural area. The 1-OH-P urinary levels of the urban (P=0.043) and rural (P=0.040) populations showed, without considering the genotypes, significant differences between smokers and non-smokers, but no significant differences were found between smokers and non-smokers among the diesel plant workers (P=0.33). Non-smoking subjects of the diesel plants and the urban area showed similar 1-OHP levels (P=0.466) which were significantly higher than those of the subjects living in the rural area (P<0.05). When 1-OH-P levels were related with genotypes, an association was observed for the CYP1A1*2A genotype, so that the diesel-exposed workers carrying the CYP1A1*2A allele showed significantly higher 1-OH-P levels than the subjects from the rural area with the same genotype (P=0.008). On the other hand, there was no significant correlation between urinary 1-OH-P levels and GSTM1 null genotype, although higher levels of the urinary metabolite were found in individuals carrying the combined CYP1A1*2A and GSTM1 null genotype (P=0.055). These results may suggest an association between levels of the exposure biomarker 1-OH-P and presence of the CYP1A1*2A genotype, a potential genetic susceptibility biomarker which might be useful in identifying individuals at higher risk among people exposed to high PAH levels in diesel exhaust.

Adult↗

PubMed2003

Gastric hypersecretion associated to iodoacetamide-induced mild gastritis in mice.

Disturbances of gastric motor, secretory and/or sensory functions are frequently associated with gastritis. The aim of this study was to characterize motor and secretory alterations associated to chemically-induced gastritis in mice. Mild gastritis was induced with 0.1% iodoacetamide administered intragastrically and added to the drinking water for a 6 days period. A significant loss of body weight and a reduction in food and water intake was observed in iodoacetamide-treated animals compared with those receiving vehicle. At the end of the treatment period, no macroscopic alterations were observed in the gastric mucosa of iodoacetamide-treated mice. However, histological sections revealed a mixed inflammatory infiltrate, with a predominance of mast cells in the submucosa; suggesting a mild gastritis. Gastric emptying rate of a nutrient solid meal was not modified in mice with gastritis compared with normal controls. In animals with gastritis, basal gastric acid secretion was increased compared with normal controls. Basal gastric acid secretion was not modified by either indomethacin or compound 48/80. Secretory response to secretagogues (pentagastrin and histamine) was enhanced during gastritis. Hypersecretory responses to both gastrin and histamine in iodoacetamide-treated mice were blocked by the mast cell stabilizer sodium cromoglycate, and enhanced by indomethacin, without affecting the secretory response in normal mice. These results suggest that mild gastritis alters gastric acid secretory responses through a mechanism related, at least partially, to mast cells activation. Moreover, prostaglandins also modulate secretory responses during mild inflammation. This animal model of gastritis might be useful to characterize pathophysiological changes and potential therapeutic targets in secretory-related gastric pathologies.

Animals↗

PubMed2003

[Clinical risk factors for postoperative proliferative vitreoretinopathy (PVR). A prospective study].

PURPOSE: To identify clinical risk factors for development of postoperative PVR, to determine the incidence of this complication and its time of onset by a prospective multicentric study. METHODS: A multicentric and prospective study of 223 patients with rhegmatogenous retinal detachment (RD) was conducted. Logistic regression analysis was used to identify risk factors for PVR among 83 variables related to preoperative, intraoperative and postoperative characteristics. RESULTS: 22 out of 223 RD developed PVR (incidence 9.9%, confidence interval 95%: 5.9-13.9). After logistic regression analysis, four variables showed an odds ratio higher than 1.0 (RD affecting 4 quadrants, cryopexy, aphakia/pseudophakia and those RD in which an encircling band was implanted). None of these factors showed a < > value lower than 0.05. Most of postoperative PVR (77.2%) appeared in the first month after surgery. CONCLUSIONS: This study establishes the incidence of PVR, and its time of onset, but it was not effective to identify clinical risk factors with a high level of confidence.

Adolescent↗

PubMed2003

Main pancreatic duct: morphlogy after acute biliary pancreatitis with magnetic resonance cholangiopancreatography after secretin stimulation.

OBJECTIVE: to assess whether a magnetic resonance cholangiopancreatography performed after an acute biliary pancreatitis leads to pancreatic morphological alterations and if secretin stimulation influences the visualization of the pancreatic tree. METHOD: forty patients with acute biliary pancreatitis, 25 female (62,5/) and 15 male (37,5/), 27 mild and 13 severe, were prospectively and consecutively studied. All patients had undergone cholecystectomy. No altered pancreatic functions were observed. Morphology of the pancreas and of the main pancreatic duct were assessed by magnetic resonance cholangiopancreatography five years after the episode of pancreatitis and a comparative study between patients and case controls was carried out. Secretin was given in 16 cases in whom the visualization of the duct was incomplete or absent. Ductal morphology before and after secretin stimulation was compared. RESULTS: significant differences were observed when the diameter and length of the main pancreatic duct were compared in patients and control cases and was completely visualized in 60% of the cases, and could be seen in all patients after secretin stimulation. The comparative statistical analysis of the length and diameter of the pancreatic duct before and after the secretin stimulation showed significant differences. CONCLUSION: acute biliary pancreatitis leads to morphological alterations, regarded as scar lesions which do not become chronic. Secretin stimulation improves the visualization of the main pancreatic duct.

Acute Disease↗

PubMed2002

Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF(2).

1. Corticotropin-releasing factor (CRF) acts in the brain to inhibit thyrotropin-releasing hormone (TRH) analogue, RX-77368-induced vagal stimulation of gastric motility. We investigated CRF receptor-mediated actions of rat urocortin (rUcn) injected intracisternally (ic) on gastric motor function. 2. Urethane-anaesthetized rats with strain gauges on the gastric corpus were injected i.c. with rUcn and 20 min later, with i.c. RX-77368. CRF antagonists were injected i.c. 10 min before rUcn. 3. RX-77368 (1.5, 3, 10, 30 and 100 ng, i.c.) dose-dependently increased corpus contractions, expressed as total area under the curve (AUC, mV min(-1)) to 2.6+/-2.5, 6.1+/-5.9, 9.8+/-2.6, 69.7+/-21.7 and 74.9+/-28.7 respectively vs 0.2+/-0.1 after i.c. saline. Ucn (1, 3 or 10 microg) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.c. saline+RX-77368. 4. The CRF(1)/CRF(2) antagonist, astressin-B (60 microg, i.c.) completely blocked i.c. rUcn (3 microg, i.c.)-induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5. The selective CRF(2) antagonist, astressin(2)-B (30, 60 or 100 microg, i.c. ) dose-dependently prevented i.c. rUCn action while the CRF(1) antagonist, NBI-27914 did not. 6. In conscious rats, rUcn (0.6 or 1 microg, i.c.) inhibited gastric emptying of an ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by astressin(2)-B. 7. These data show that i.c. rUcn acts through CRF(2) receptors to inhibit central vagal gastric contractile response and postoprandial emptying.

Animals↗