The American journal of physiology
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Comparative Study
Signal transduction pathways via guanylin and uroguanylin in stomach and intestine.
Guanylin and uroguanylin are peptides that activate receptor guanylate cyclases (GCs) and elicit increased intestinal secretion. Bacteria that cause traveler's diarrhea produce heat-stable toxins (STs) that mimic this action. Investigation of the distribution and identity of receptor GCs in the gastrointestinal tract of rats revealed that receptors were localized to epithelial cells in stomach and intestine. ⋯ Uroguanylin and guanylin mRNAs were detected in stomach and intestine. Uroguanylin mRNA was most abundant in small intestine, whereas guanylin mRNA was highest in large intestine. Thus the stomach and intestine are targets for regulation of transport by guanylin and uroguanylin via cGMP.
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This study tests the hypothesis that a 2-4 degrees C reduction in myocardial temperature, obtained by using topical regional hypothermia (TRH), reduces infarct size. Anesthetized rabbits received coronary artery occlusion and reperfusion. We cooled hearts in the TRH group by applying an ice bag directly over the risk zone; the control group received no intervention. ⋯ Infarct size closely correlated with MT in the risk region at the time of occlusion. In a second protocol in which all hearts were paced, infarct size was 21% of the risk region in TRH hearts compared with 44% in controls. These results strongly support the important role of MT in the progression of necrosis and demonstrate that the application of local cooling to the risk region profoundly reduces myocardial infarct size.
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We assessed local cerebral glucose metabolism (lCMRGlc) and blood flow (lCBF) interrelationships in the first hour after parasagittal fluid-percussion head injury (FPI) in rats. Matched series were studied autoradiographically for lCMRGlc and lCBF with 2-[14C]deoxyglucose and 14C-labeled iodoantipyrine, respectively. Three-dimensional autoradiographic-image mapping was to generate average data sets from which a mean ICMRGlc-to-lCBF ratio data set was derived. lCBF in neocortical regions ipsilateral to the trauma were depressed, on average, by 44% compared with sham-FPI rats, whereas contralateral lCBF values were not altered. ⋯ The extent of metabolism-flow uncoupling, on average, amounted to 2.5-fold in the ipsilateral hippocampus and neocortex and 1.7-fold contralaterally. The loci of pronounced metabolism-flow dissociation corresponded closely to the previously documented histological distribution of neuronal necrosis. Our findings resemble events occurring in the acute focal ischemic penumbra and suggest that similar injury mechanisms may be operative.
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We examined the effect of oropharyngeal stimulation on thirst, secretion of arginine vasopressin ([AVP]p), and fluid intake in six healthy adults after dehydration (28.6 +/- 1.4 ml/kg water loss) induced by mild exercise in the heat (2 h, 38 degrees C, relative humidity < 30%). Subjects performed three identical dehydration protocols followed by 75 min of rehydration at 27 degrees C consisting of 1) ad libitum drinking (Con), 2) infusion of a similar volume of water directly into the stomach via a nasogastric tube (Inf) during the first 25 min followed by combined Inf and ad libitum drinking during the remaining 50 min of rehydration; or 3) ad libitum drinking with simultaneous extraction of ingested fluid via a nasogastric tube (Ext). Plasma osmolality (Posm), [AVP]p, fluid intake, and thirst perceptions were measured throughout. ⋯ Reflex inhibition of [AVP]p and thirst occurred within 5 min of rehydration in Con and Ext (P < 0.05) but not during Inf, supporting the hypothesis that oropharyngeal reflexes modulate osmotically stimulated thirst and [AVP]p. However, the reduction in [AVP]p during the first 5 min of Ext (-1.1 +/- 0.3 pg/ml) was less than that seen during Con (-2.1 +/- 0.4 pg/ml), suggesting that oropharyngeal stimulation is not the only factor contributing to the rapid reduction in [AVP]p during the first 5 min of drinking. During Con, subjects ingested 20.0 +/- 2.0 ml/kg of water but only drank 15% more (31.3 +/- 7.1 ml/kg) during Ext, demonstrating a clear role of oropharyngeal metering in limiting total fluid intake in humans in the presence of a persistently high dipsogenic drive.
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The present studies investigated the significance of glucoprivic metabolic signals, particularly those of central origin, to the regulation of pituitary luteinizing hormone (LH). Groups of gonadectomized (GDX) adult male rats were treated with 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, by either intravenous (50, 100, or 200 mg/kg) or intracerebroventricular (5, 20, or 100 microg/rat) administration. Systemic drug treatment caused a significant decrease in mean plasma LH levels compared with saline-treated controls. ⋯ In summary, treatment of GDX rats with the glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic signaling of cellular glucose oxidation is of physiological importance to the regulation of pituitary hormone secretion. Findings that plasma LH was diminished in animals treated intracerebroventricularly with 2-DG implicate central glucoprivic receptors in neuroendocrine mechanisms governing the reproductive endocrine axis. Attenuation of 2-DG-induced decreases in circulating LH by opioid receptor antagonists suggests that these receptors, particularly the mu-subtype, mediate central effects of glucoprivation on circulating LH.