American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · May 2009
Bladder hyperactivity and increased excitability of bladder afferent neurons associated with reduced expression of Kv1.4 alpha-subunit in rats with cystitis.
Hyperexcitability of C-fiber bladder afferent pathways has been proposed to contribute to urinary frequency and bladder pain in chronic bladder inflammation including interstitial cystitis. However, the detailed mechanisms inducing afferent hyperexcitability after bladder inflammation are not fully understood. Thus, we investigated changes in the properties of bladder afferent neurons in rats with bladder inflammation induced by intravesical application of hydrochloric acid. ⋯ The expression of voltage-gated K(+) Kv1.4 alpha-subunits, which can form A-type K(+) channels, was reduced in bladder afferent neurons from cystitis rats. These data suggest that bladder inflammation increases bladder afferent neuron excitability by decreasing expression of Kv1.4 alpha-subunits. Similar changes in capsaicin-sensitive C-fiber afferent terminals may contribute to bladder hyperactivity and hyperalgesia due to acid-induced bladder inflammation.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Apr 2009
The transcription factor, glial cell missing 2, is involved in differentiation and functional regulation of H+-ATPase-rich cells in zebrafish (Danio rerio).
H(+)-ATPase-rich (HR) cells in zebrafish are known to be involved in acid secretion and Na(+) uptake mechanisms in zebrafish gills/skin; however, little is known about how HR cells are functionally regulated. In the present work, we studied the roles of Drosophila glial cell missing (gcm), a cell fate-related transcription factor, in the differentiation and functional regulation of zebrafish HR cells. Zebrafish gcm2 (zgcm2) was found to begin expression in zebrafish embryos at 10 h postfertilization (hpf), and to be extensively expressed in gills but only mildly so in eyes, heart, muscles, and testes. ⋯ Knockdown of zgcm2 with a specific morpholino oligonucleotide caused the complete disappearance of HR cells with a concomitant decrease in H(+) activity at the apical surface of HR cells, but it did not affect the occurrence of Na(+)-K(+)-ATPase-rich cells. A decrease in the H(+)-ATPase subunit A (zatp6v1a) expression and no change in zgcm2 expression in zebrafish gills were seen from 12 h to 3 days after transfer to acidic fresh water, but a compensatory stimulation in the expressions of both genes appeared 4 days post-transfer. In conclusion, functional regulation of HR cells is probably achieved by enhancing cell differentiation via zGCM2 activation.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Apr 2009
Multiple sweet receptors and transduction pathways revealed in knockout mice by temperature dependence and gurmarin sensitivity.
Sweet taste transduction involves taste receptor type 1, member 2 (T1R2), taste receptor type 1, member 3 (T1R3), gustducin, and TRPM5. Because knockout (KO) mice lacking T1R3, gustducin's Galpha subunit (Galphagust), or TRPM5 exhibited greatly reduced, but not abolished responses of the chorda tympani (CT) nerve to sweet compounds, it is likely that multiple sweet transduction pathways exist. That gurmarin (Gur), a sweet taste inhibitor, inhibits some but not all mouse CT responses to sweet compounds supports the existence of multiple sweet pathways. ⋯ All three KO mice exhibited no detectable responses to SC45647, and their responses to saccharin displayed neither GS nor a TDI. For all three KO mice, the lingual application of pronase, another sweet response inhibitor, almost fully abolished responses to sucrose and glucose but did not affect responses to saccharin. These results provide evidence for 1) the existence of multiple transduction pathways underlying responses to sugars: a T1R3-independent GS pathway for sucrose and glucose, and a TRPM5-independent temperature sensitive GS pathway for glucose; 2) the requirement for Galphagust in GS sweet taste responses; and 3) the existence of a sweet independent pathway for saccharin, in mouse taste cells on the anterior tongue.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Apr 2009
Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx.
We previously determined that ghrelin synthesis was downregulated after burn injury and that exogenous ghrelin retained its ability both to stimulate food intake and to restore plasma growth hormone levels in burned rats. These observations and the finding that anabolic hormones can attenuate skeletal muscle catabolism led us to investigate whether ghrelin could attenuate burn-induced skeletal muscle protein breakdown in rats. These studies were performed in young rats (50-60 g) 24 h after approximately 30% total body surface area burn injury. ⋯ Moreover, ghrelin normalized plasma glucocorticoid levels, which were elevated after burn. Expression of the muscle-specific ubiquitin-ligating enzyme (E3) ubiquitin ligases MuRF1 and MAFbx were markedly elevated in both EDL and gastrocnemius and were normalized by ghrelin. These results suggest that ghrelin is a powerful anticatabolic compound that reduces skeletal muscle protein breakdown through attenuating multiple burn-induced abnormalities.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Mar 2009
Reactive oxygen species-dependent endothelin signaling is required for augmented hypoxic sensory response of the neonatal carotid body by intermittent hypoxia.
We previously reported that intermittent hypoxia (IH) augments hypoxic sensory response (HSR) and increases the number of glomus cells in neonatal carotid bodies. In the present study, we tested the hypothesis that recruitment of endothelin-1 (ET-1) signaling by reactive oxygen species (ROS) plays a critical role in IH-evoked changes in neonatal carotid bodies. Experiments were performed on neonatal rats exposed either to 10 days of IH (P0-P10; 8 h/day) or to normoxia. ⋯ Systemic administration of manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 5 mg/kg ip), a scavenger of O(2)(*-), prevented IH-induced elevation of ROS, basal release of ET-1, upregulation of ET(A) mRNA, and augmented HSR. In striking contrast, MnTMPyP treatment had no significant effect on IH-induced hyperplasia of glomus cells. These results demonstrate that IH-evoked increase in HSR involve a ROS-mediated increase in basal ET-1 release and upregulation of ET(A) receptor mRNA.