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Previous investigations have demonstrated the therapeutic advantages of extremely low-frequency electromagnetic fields (ELF-EMFs) in mitigating inflammation and influencing biological processes. We aimed to shed light on the effects of ELF-EMF on recovery rate following high-intensity exercise. Nine male athletes (26.7 ± 6.0 years; 69.6 ± 7.7 kg, VO2peak 57.3 ± 6.8 mL/kg/min) completed five visits in a double-blinded crossover design, performing two consecutive testing days, following a ventilatory thresholds assessment. Following 62 min of high-intensity cycling, participants lay on an ELF-EMF mattress under active (A) and non-active (NA) conditions, immediately post protocol and during the night. Physical performance and blood markers were assessed at baseline and at 60 min (60 P) and 24 h (24 H) post-protocol. The A-condition demonstrated a notable reduction in interleukin-10 (IL-10) concentrations (mean difference = −88%, p = 0.032) and maximal isometric strength of the quadriceps muscles (mean difference = ~8%, p = 0.045) compared to the NA-condition between 60 P and 24 H. In a sensitivity analysis, the A-condition revealed that younger athletes who possessed lower fat mass experienced attenuated inflammation and biochemical responses and improved physical performance. In conclusion, ELF-EMF showed no significant overall effects on performance and inflammation after intense cycling among athletes. Post-hoc analysis revealed modest benefits of ELF-MLF, suggesting a context-dependent impact. Further research with a larger sample size and multiple sessions is needed to confirm the recovery potential of ELF-EMF. [ABSTRACT FROM AUTHOR]

Sceletium tortuosum (ST) is a South African plant that has been reported to promote a sense of well-being in healthy individuals and used in treating people with anxiety, stress, or depression. These studies have been conducted in middle-aged and older adults, but no investigations have been performed in a healthy, young adult population. Thus, the purpose of this study was to examine the effect of 8 days of ST extract (25-mg) supplementation on changes in reactive agility, visual tracking, and mood. Sixty recreationally trained men (n = 48) and women (n = 12), between 20 and 35 years, were randomly assigned to 1 of 2 groups: ST or placebo (PL). Subjects were tested on 2 occasions: before supplementation and 2-hours after supplementation on day 8. Subjects completed a subjective questionnaire to assess alertness and energy using a visual analog scale (VAS). In addition, subjects completed the Profile of Mood States questionnaire and performed reactive agility and visual tracking assessments. Significant improvements were noted for ST in complex reactive performance that required subjects to respond to repeated visual stimuli with a cognitive load compared with PL. However, no significant changes were noted between the groups in either VAS or total mood score. In addition, no differences were observed in simple reaction assessments. The results of this study demonstrate an ergogenic benefit in complex reactive tasks that include a cognitive load. However, in this subject population studied, no benefits in mood were observed. [ABSTRACT FROM AUTHOR]

ATP release from urinary bladder is vital for afferent signaling. The aims of this study were to localize calcium homeostasis modulator 1 (CALHM1) and pannexin-1 expression and to determine their involvement in mediating ATP release in the bladder. To determine gene expression and cellular distribution, PCR and immunohistochemistry were performed, respectively, in the porcine bladder. CALHM1 and pannexin-1-mediated ATP release in response to hypotonic solution (0.45% NaCl)-induced stretch, and extracellular Ca2+ depletion ([Ca2+]0) was measured in isolated urothelial, suburothelial, and detrusor muscle cells. CALHM1 and pannexin-1 mRNA and immunoreactivity were detected in urothelial, suburothelial, and detrusor muscle layers, with the highest expression on urothelium. Hypotonic stretch caused a 2.7-fold rise in ATP release from all three cell populations (P < 0.01), which was significantly attenuated by the pannexin-1 inhibitor, 10Panx1, and by the CALHM1 antibody. Brefeldin A, a vesicular transport inhibitor, and ruthenium red, a nonselective CALHM1 channel blocker, also significantly inhibited stretch-mediated ATP release from urothelial cells. [Ca2+]0 caused a marked, but transient, elevation of extracellular ATP level in all three cell populations. CALHM1 antibody and ruthenium red inhibited [Ca2+]0-induced ATP release from urothelial cells, but their effects on suburothelial and detrusor cells were insignificant. 10Panx1 showed no significant inhibition of [Ca2+]0-induced ATP release in any types of cells. The results presented here provide compelling evidence that pannexin-1 and CALHM1, which are densely expressed in the porcine bladder, function as ATP release channels in response to bladder distension. Modulation of extracellular Ca2+ may also regulate ATP release in the porcine bladder through voltage-gated CALHM1 ion channels. [ABSTRACT FROM AUTHOR]

The tachykinin peptide bufokinin, isolated from the cane toad intestine, is important in intestinal and cardiovascular regulation in the toad. In this study, three tachykinin NKk-like receptor isoforms, bNK1-A, bNK1-B, and bNK1-C, encoding proteins of 309, 390, and 371 amino acids, respectively, were cloned from the toad brain and intestine. These isoforms differ only at the intracellular COOH terminus. The bNK1-A and bNK1-B isoforms are similar to the truncated and full-length forms of the mammalian NK1 receptor, whereas bNK1-C is unique and does not correspond to any previously described receptor. RT-PCR studies demonstrated that three isoform transcripts are widely distributed in the toad with high expression in gut, spinal cord, brain, lung, and skeletal muscle. When expressed in COS-7 cells, bufokinin showed similar high affinity (IC50 0.6-0.8 nM) in competing for 125I-labeled Bolton-Hunter bufokinin binding at all receptors, but the binding affinities of substance P (SP) and neurokinin A (NKA) were very different at each isoform. When expressed in Xenopus oocytes, the truncated isoform, bNK1-A, was inactive, whereas bNK1-B and bNK1-C produced changes in chloride current when stimulated by tachykinins (minimum concentrations: bufokinin, 0.1 nM; SP, 1 nM; and NKA, 10 nM). A marked desensitization of the response was seen to subsequent applications of tachykinins, as experienced by the mammalian NK1 receptor. In summary, our study describing three isoforms of NK1-like receptor from the toad suggests that the alternative splicing of NK1 receptor is a physiologically conserved mechanism and raises a fundamental question as to the physiological role of each isoform. [ABSTRACT FROM AUTHOR]

L5466 --> Chronic stress often elicits neuronal, hormonal, and immune responses. Long term hypercapnia is a respiratory stressor linked with sleep apnea, sudden infant death syndrome (SIDS) and chronic obstructive pulmonary disease (COPD), however, mechanisms of central respiratory dysfunction in these conditions are unclear. We aimed to explore the neuroinflammatory responses to hypercapnia in key brain respiratory regions. We tested the hypothesis that long‐term exposure to 8% CO2 activates the releaseof brain stress hormone corticosterone (CORT) in the circulation which may contribute to inflammation in brainstem circuits that regulate CO2‐stimulated breathing. Age‐matched adult male C57BL/6J mice (n=10 mice/group) were exposed to hypercapnia (8% CO2; balance room air) in the short‐term (6 hours) or long‐term (10 or 14 days), or room air (control) conditions.Following anesthesia, plasma samples were collected for corticosterone (CORT) assay and brain tissues including cerebellum, hypothalamus, the nucleus of the solitary tract (NTS), rostral and caudal retrotrapezoid nucleus (rRTN, cRTN) were micro‐dissected and processed for cytokine assays. Plasma CORT levels were not different between hypercapnia and room air groups in the short‐term, but a significantly higher CORT level (p < 0.01, 2 way ANOVA) was observed following 10 days of exposure to hypercapnia compared to control conditions. CORT level returned to baseline following 14 days of hypercapnia compared to control (14 days room air) conditions. In the brain, the pro‐inflammatory cytokine interleukin‐1β (IL‐1β) was raised in the cerebellum (p < 0.01, 2 way ANOVA) following 6 hours but not 10 days of hypercapnia exposure, compared to control conditions. In the hypothalamus and cRTN, IL‐1β was unaltered at the 6 hours time point, significantly upregulated (p < 0.05, p < 0.01, 2 way ANOVA) at 10 days of hypercapnia exposure, compared to controls. In these brain regions, IL‐1β levels returned to baseline after 14 days hypercapnia exposure time point. There was no change in IL‐1β in the rRTN and NTS following 6 hours, 10 days, and 14 days of hypercapnia, compared to controls. Taken together, the level of plasma CORT positively correlates to brain IL‐1β during long‐term hypercapnia. These results suggest that hypercapnia activates a physiological stress response, and the associated brain inflammation depends on the duration of hypercapnia exposure. We propose that the stress and inflammatory adaptive responses observed are part of compensatory mechanisms following long‐term hypercapnia. The cellular source and underlying mechanisms of interactions between plasma CORT and brain IL‐1β are under investigation. [ABSTRACT FROM AUTHOR]

Background and Purpose: The physiological role of vascular β3 -adrenoceptors is not fully understood. Recent evidence suggests cardiac β3 -adrenoceptors are functionally effective after down-regulation of β1 /β2 -adrenoceptors. The functional interaction between the β3 -adrenoceptor and other β-adrenoceptor subtypes in rat striated muscle arteries was investigated.Experimental Approach: Studies were performed in cremaster muscle arteries isolated from male Sprague-Dawley rats. β-adrenoceptor expression was assessed through RT-PCR and immunofluorescence. Functional effects of β3 -adrenoceptor agonists and antagonists and other β-adrenoceptor ligands were measured using pressure myography.Key Results: All three β-adrenoceptor subtypes were present in the endothelium of the cremaster muscle artery. The β3 -adrenoceptor agonists mirabegron and CL 316,243 had no effect on the diameter of pressurized (70 mmHg) cremaster muscle arterioles with myogenic tone, while the β3 -adrenoceptor agonist SR 58611A and the nonselective β-adrenoceptor agonist isoprenaline caused concentration-dependent dilation. In the presence of β1/2 -adrenoceptor antagonists nadolol (10 μM), atenolol (1 μM) and ICI 118,551 (0.1 μM) both mirabegron and CL 316,243 were effective in causing vasodilation and the potency of SR 58611A was enhanced, while responses to isoprenaline were inhibited. The β3 -adrenoceptor antagonist L 748,337 (1 μM) inhibited vasodilation caused by β3 -adrenoceptor agonists (in the presence of β1/2 -adrenoceptor blockade), but L 748,337 had no effect on isoprenaline-induced vasodilation.Conclusion and Implications: All three β-adrenoceptor subtypes were present in the endothelium of the rat cremaster muscle artery, but β3 -adrenoceptor mediated vasodilation was only evident after blockade of β1/2 -adrenoceptors. This suggests constitutive β1/2 -adrenoceptor activity inhibits β3 -adrenoceptor function in the endothelium of skeletal muscle resistance arteries. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) was recently found in the enteric nervous system, where its role is unclear. We aimed to identify which enteric neuronal structures express CFTR, whether CFTR modulates enteric neurotransmission and if altered CFTR expression is associated with slow transit constipation (STC).Methods: Immunofluorescence double labeling was performed to localize CFTR with various neuronal and glial cell markers in the human colon. The immunoreactivity (IR) of CFTR and choline acetyltransferase (ChAT) on myenteric plexus of control and STC colon was quantitatively analyzed. In control colonic muscle strips, electrical field stimulation (EFS) evoked contractile responses and the release of acetylcholine (ACh) was measured in the presence of the CFTR channel inhibitor, CFTR(inh)-172.Results: CFTR-IR was densely localized to myenteric ganglia, where it was co-localized with neuronal markers HuC/D and β-tubulin, and glial marker S-100 but little with glial fibrillary acidic protein. Vesicular ACh transport was almost exclusively co-localized with CFTR, but neurons expressing nitric oxide synthase were CFTR negative. Significant reductions of CFTR-IR (P < 0.01) and ChAT-IR (P < 0.05) were observed on myenteric ganglia of STC compared to control. Pre-treatment of colonic muscle strips with CFTR(inh)-172 (10 µM) significantly inhibited EFS-evoked contractile responses (P < 0.01) and ACh release (P < 0.05).Conclusions: Co-localization of CFTR-IR with cholinergic markers, inhibition of EFS-induced colonic muscle contractility and ACh release by CFTR(inh)-172 suggest that CFTR modulates enteric cholinergic neurotransmission. The downregulation of CFTR and ChAT in myenteric ganglia of STC correlated with the impaired contractile responses to EFS. [ABSTRACT FROM AUTHOR]