The amiloride-insensitive salt taste receptor is the predominant transducer of salt taste in some mammalian species, including humans. The physiological, pharmacological and biochemical properties of the amiloride-insensitive salt taste receptor were investigated by RT-PCR, by the measurement of unilateral apical Na + fluxes in polarized rat fungiform taste receptor cells and by chorda tympani taste nerve recordings. The chorda tympani responses to NaCl, KCl, NH 4 Cl and CaCl 2 were recorded in Sprague-Dawley rats, and in wild-type and vanilloid receptor-1 (VR-1) knockout mice. The chorda tympani responses to mineral salts were monitored in the presence of vanilloids (resiniferatoxin and capsaicin), VR-1 antagonists (capsazepine and SB-366791), and at elevated temperatures. The results indicate that the amiloride-insensitive salt taste receptor is a constitutively active non-selective cation channel derived from the VR-1 gene. It accounts for all of the amiloride-insensitive chorda tympani taste nerve response to Na + salts and part of the response to K + , NH 4 + and Ca 2+ salts. It is activated by vanilloids and temperature (> 38• C), and is inhibited by VR-1 antagonists. In the presence of vanilloids, external pH and ATP lower the temperature threshold of the channel. This allows for increased salt taste sensitivity without an increase in temperature. VR-1 knockout mice demonstrate no functional amiloride-insensitive salt taste receptor and no salt taste sensitivity to vanilloids and temperature. We conclude that the mammalian non-specific salt taste receptor is a VR-1 variant.

The intestinal barrier is complex and consists of multiple layers, and it provides a physical and functional barrier to the transport of luminal contents to systemic circulation. While the epithelial cell layer and the outer/inner mucin layer constitute the physical barrier and are often referred to as the intestinal barrier, intestinal alkaline phosphatase (IAP) produced by epithelial cells and antibacterial proteins secreted by Panneth cells represent the functional barrier. While antibacterial proteins play an important role in the host defense against gut microbes, IAP detoxifies bacterial endotoxin lipopolysaccharide (LPS) by catalyzing the dephosphorylation of the active/toxic Lipid A moiety, preventing local inflammation as well as the translocation of active LPS into systemic circulation. The causal relationship between circulating LPS levels and the development of multiple diseases underscores the importance of detailed examination of changes in the “layers” of the intestinal barrier associated with disease development and how this dysfunction can be attenuated by targeted interventions. To develop targeted therapies for improving intestinal barrier function, it is imperative to have a deeper understanding of the intestinal barrier itself, the mechanisms underlying the development of diseases due to barrier dysfunction (eg, high circulating LPS levels), the assessment of intestinal barrier function under diseased conditions, and of how individual layers of the intestinal barrier can be beneficially modulated to potentially attenuate the development of associated diseases. This review summarizes the current knowledge of the composition of the intestinal barrier and its assessment and modulation for the development of potential therapies for barrier dysfunction-associated diseases.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with a significant economic burden related to hospital admissions for exacerbations. One of the primary treatment modalities for COPD is medications delivered through breath-actuated dry powdered inhalers (DPIs). For users to successfully receive inhaled medication, they must inhale with enough flow to overcome the internal resistance of the device, leading to deaggregation of the medication powder. Peak inspiratory flow rate (PIFR) is the maximal flow rate obtained during an inspiratory maneuver. PIFR measurement can be impacted by the internal resistance of the device, which varies with device design. Many devices require a PIFR >60 L/min for adequate medication dispersal, while others appear to have adequate drug deaggregation with a PIFR >30 L/min. Studies have shown PIFRs are reduced among females and decrease with age, without a clear correlation between forced expiratory volume in 1 second and PIFR. PIFR can be reduced at the time of COPD exacerbation. Recent data suggest that reduced PIFR may be associated with worse COPD-related symptom burden, increased odds of COPD-related hospital readmissions, and improved responsiveness to nebulized therapy. This review article aims to examine the physiology and clinical correlations of PIFR, as well as review published studies related to PIFR with DPIs used to treat COPD.

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