American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Aug 2008
Hydrogen sulfide as an oxygen sensor in trout gill chemoreceptors.
O2 chemoreceptors elicit cardiorespiratory reflexes in all vertebrates, but consensus on O2-sensing signal transduction mechanism(s) is lacking. We recently proposed that hydrogen sulfide (H2S) metabolism is involved in O2 sensing in vascular smooth muscle. Here, we examined the possibility that H2S is an O2 sensor in trout chemoreceptors where the first pair of gills is a primary site of aquatic O2 sensing and the homolog of the mammalian carotid body. ⋯ In isolated zebrafish neuroepithelial cells, the putative chemoreceptive cells of fish, both hypoxia and H2S, produced a similar approximately 10-mV depolarization. These studies are consistent with H2S involvement in O2 sensing/signal transduction pathway(s) in chemoreceptive cells, as previously demonstrated in vascular smooth muscle. This novel mechanism, whereby H2S concentration ([H2S]) is governed by the balance between constitutive production and oxidation, tightly couples tissue [H2S] to PO2 and may provide an exquisitely sensitive, yet simple, O2 sensor in a variety of tissues.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Aug 2008
Moderate zinc restriction during fetal and postnatal growth of rats: effects on adult arterial blood pressure and kidney.
Intrauterine and postnatal zinc restriction may result in an adverse environment for the development of cardiovascular and renal systems. This study evaluated the effects of moderate zinc deficiency during fetal life, lactation, and/or postweaning growth on systolic blood pressure, renal function, and morphology in adult life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy up to weaning. ⋯ These animals showed signs of renal fibrosis, proteinuria, increased renal apoptosis, and higher lipid peroxidation end products. A control diet during postweaning growth did not totally overcome renal oxidative stress damage, apoptosis, and fibrosis induced by zinc deficiency before weaning. In conclusion, zinc deficiency during a critical period of renal development and maturation could induce functional and morphological alterations that result in elevated blood pressure and renal dysfunction in adult life.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Aug 2008
Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss.
Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. ⋯ We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Aug 2008
Licking and gaping elicited by microstimulation of the nucleus of the solitary tract.
Intraoral infusions of bitter tastants activate expression of the immediate-early gene c-Fos in neurons located in the medial third of the rostral nucleus of the solitary tract (rNST). The distribution of these neurons is distinct from that activated by sour or sweet stimuli. Bitter stimuli are also distinctive because of their potency for eliciting gaping, an oral reflex that functions to actively reject potentially toxic substances. ⋯ The results indicated some topographic organization in sites effective for evoking gaping, but, in direct conflict with the hypothesis, lateral sites farther from bitter-evoked FLI were more effective than medial sites centered closer to FLI-expressing neurons. The gape-effective sites resemble locations of bitter-responsive neurons recently observed in neurophysiological recordings. These results indicate that bitter-responsive rNST neurons critical for triggering gaping may not express FLI and imply an alternate function for bitter-responsive neurons that do.