Calcium-sensing receptor (CaSR) modulates ocular surface chloride transport and its inhibition promotes ocular surface hydration.

Purpose: Ocular surface hydration is critical for eye health and its impairment can lead to dry eye disease. Extracellular calcium-sensing receptor (CaSR) is regulator of ion transport in epithelial cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel. CFTR is also a major ion channel in ocular surface epithelia, however the roles of CaSR in ocular surface are not well studied.

Mg2+ supplementation treats secretory diarrhea in mice by activating calcium-sensing receptor in intestinal epithelial cells.

Cholera is a global health problem with no targeted therapies. The Ca2+-sensing receptor (CaSR) is a regulator of intestinal ion transport and a therapeutic target for diarrhea, and Ca2+ is considered its main agonist. We found that increasing extracellular Ca2+ had a minimal effect on forskolin-induced Cl- secretion in human intestinal epithelial T84 cells.

Anserine is expressed in human cardiac and skeletal muscles.

We evaluated whether anserine, a methylated analog of the dipeptide carnosine, is present in the cardiac and skeletal muscles of humans and whether the CARNMT1 gene, which encodes the anserine synthesizing enzyme carnosine-N-methyltransferase, is expressed in human skeletal muscle. We found that anserine is present at low concentrations (low micromolar range) in both cardiac and skeletal muscles, and that anserine content in skeletal muscle is ~15 times higher than in cardiac muscle (cardiac muscle: 10.1 ± 13.

Small molecule inhibitors of intestinal epithelial anion exchanger SLC26A3 (DRA) with a luminal, extracellular site of action.

The anion exchanger protein SLC26A3 (down-regulated in adenoma, DRA) is expressed in the luminal membrane of intestinal epithelial cells in colon, where it facilitates the absorption of Cl and oxalate. We previously identified a 4,8-dimethylcoumarin class of SLC26A3 inhibitors that act from the SLC26A3 cytoplasmic surface, and demonstrated their efficacy in mouse models of constipation and hyperoxaluria. Here, screening of 50,000 new compounds and 1740 chemical analogs of active compounds from the primary screen produced five novel classes of SLC26A3-selective inhibitors (1,3-dioxoisoindoline-amides; N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamides; thiazolo-pyrimidin-5-ones; 3-carboxy-2-phenylbenzofurans and benzoxazin-4-ones) with IC down to 100 nM.

Physiological Roles of Carnosine in Myocardial Function and Health.

Carnosine is a pleiotropic histidine-containing dipeptide synthesized from β-alanine and l-histidine, with the intact dipeptide and constituent amino acids being available from the diet. The therapeutic application of carnosine in myocardial tissue is promising, with carnosine playing a potentially beneficial role in both healthy and diseased myocardial models. This narrative review discusses the role of carnosine in myocardial function and health, including an overview of the metabolic pathway of carnosine in the myocardial tissue, the roles carnosine may play in the myocardium, and a critical analysis of the literature, focusing on the effect of exogenous carnosine and its precursors on myocardial function.

Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model.

Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H buffering, regulation of Ca transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function.

The role of chronic muscle (in)activity on carnosine homeostasis: a study with spinal cord-injured athletes.

To examine the role of chronic (in)activity on muscle carnosine (MCarn) and how chronic (in)activity affects MCarn responses to β-alanine supplementation in spinal cord-injured athletes, 16 male athletes with paraplegia were randomized (2:1 ratio) to receive β-alanine ( = 11) or placebo (PL, = 5). They consumed 6.4 g/day of β-alanine or PL for 28 days.

Kinetics of Muscle Carnosine Decay after β-Alanine Supplementation: A 16-wk Washout Study.

Purpose: This study aimed to describe the kinetics of carnosine washout in human skeletal muscle over 16 wk.

Methods: Carnosine washout kinetics were studied in 15 young, physically active omnivorous men randomly assigned to take 6.4 g·d-1 of β-alanine (n = 11) or placebo (n = 4) for 8 wk.

Number of high-protein containing meals correlates with muscle mass in pre-frail and frail elderly.

Background: Aging is accompanied by the inability to optimally respond to anabolic stimulus of nutrition, with consequent loss of muscle mass and functionality. It has been speculated that not only total protein intake, but also the per meal protein dose may have important implications to protein balance and, hence, muscle mass in middle-aged and older adults, but evidence is lacking in a more vulnerable population such as the frail elderly. The aim was to investigate possible associations between total protein intake and its per meal dose with multiple measures of muscle mass, strength, and functionality in a cohort of pre-frail and frail elderly individuals.

Insulin does not stimulate β-alanine transport into human skeletal muscle.

To test whether high circulating insulin concentrations influence the transport of β-alanine into skeletal muscle at either saturating or subsaturating β-alanine concentrations, we conducted two experiments whereby β-alanine and insulin concentrations were controlled. In , 12 men received supraphysiological amounts of β-alanine intravenously (0.11 g·kg·min for 150 min), with or without insulin infusion.

"Despite being an athlete, I am also a human-being": Male elite gymnasts' reflections on food and body image.

Our aim was to investigate the prevalence of symptoms related to eating disorders, disordered eating and body image perception, and attitudes toward eating in a group of elite male artistic gymnastics. Seventeen athletes took part in this quali-quantitative, cross-sectional study. Presence of eating disorders symptoms, and body image perception and satisfaction were assessed using validated questionnaires.

The molecular structure of β-alanine is resistant to sterilising doses of gamma radiation.

β-alanine is the rate-limiting point for the endogenous synthesis of carnosine in skeletal muscle. Carnosine has a wide range of implications for health, normal function and exercise performance. Whilst the physiological relevance of carnosine to different tissues remains enigmatic, β-alanine administration is a useful strategy to investigate the physiological roles of carnosine in humans.

Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation.

This study investigates the influence of habitual caffeine intake on aerobic exercise-performance responses to acute caffeine supplementation. A double-blind, crossover, counterbalanced study was performed. Forty male endurance-trained cyclists were allocated into tertiles, according to their daily caffeine intake: low (58 ± 29 mg/d), moderate (143 ± 25 mg/d), and high (351 ± 139 mg/d) consumers.

Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years.