Search

Purpose: Postexercise recovery rate is a vital component of designing personalized training protocols and rehabilitation plans. Tracking exercise‐induced muscle damage and recovery requires sensitive tools that can probe the muscles' state and composition noninvasively. Methods: Twenty‐four physically active males completed a running protocol consisting of a 60‐min downhill run on a treadmill at −10% incline and 65% of maximal heart rate. Quantitative mapping of MRI T2 was performed using the echo‐modulation‐curve algorithm before exercise, and at two time points: 1 h and 48 h after exercise. Results: T2 values increased by 2%–4% following exercise in the primary mover muscles and exhibited further elevation of 1% after 48 h. For the antagonist muscles, T2 values increased only at the 48‐h time point (2%–3%). Statistically significant decrease in the SD of T2 values was found following exercise for all tested muscles after 1 h (16%–21%), indicating a short‐term decrease in the heterogeneity of the muscle tissue. Conclusion: MRI T2 relaxation time constitutes a useful quantitative marker for microstructural muscle damage, enabling region‐specific identification for short‐term and long‐term systemic processes, and sensitive assessment of muscle recovery following exercise‐induced muscle damage. The variability in T2 changes across different muscle groups can be attributed to their different role during downhill running, with immediate T2 elevation occurring in primary movers, followed by delayed elevation in both primary and antagonist muscle groups, presumably due to secondary damage caused by systemic processes. [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 N[K.sub.1]-like receptor isoforms, bN[K.sub.1]-A, bN[K.sub.1]-B, and bN[K.sub.1]-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 bN[K.sub.1]-A and bN[K.sub.1]-B isoforms are similar to the truncated and full-length forms of the mammalian N[K.sub.1] receptor, whereas bN[K.sub.1]-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 (I[C.sub.50] 0.6-0.8 nM) in competing for [sup.125]I-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, bN[K.sub.1]-A, was inactive, whereas bN[K.sup.1]-B and bN[K.sub.1]-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 N[K.sub.1] receptor. In summary, our study describing three isoforms of N[K.sub.1]-like receptor from the toad suggests that the alternative splicing of N[K.sub.1] receptor is a physiologically conserved mechanism and raises a fundamental question as to the physiological role of each isoform. bufokinin; tachykinin receptors; sequencing and cloning; Xenopus oocyte expression; amphibian

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]

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]

Purpose: Postexercise recovery rate is a vital component of designing personalized training protocols and rehabilitation plans. Tracking exercise-induced muscle damage and recovery requires sensitive tools that can probe the muscles' state and composition noninvasively., Methods: Twenty-four physically active males completed a running protocol consisting of a 60-min downhill run on a treadmill at -10% incline and 65% of maximal heart rate. Quantitative mapping of MRI T 2 was performed using the echo-modulation-curve algorithm before exercise, and at two time points: 1 h and 48 h after exercise., Results: T 2 values increased by 2%-4% following exercise in the primary mover muscles and exhibited further elevation of 1% after 48 h. For the antagonist muscles, T 2 values increased only at the 48-h time point (2%-3%). Statistically significant decrease in the SD of T 2 values was found following exercise for all tested muscles after 1 h (16%-21%), indicating a short-term decrease in the heterogeneity of the muscle tissue., Conclusion: MRI T 2 relaxation time constitutes a useful quantitative marker for microstructural muscle damage, enabling region-specific identification for short-term and long-term systemic processes, and sensitive assessment of muscle recovery following exercise-induced muscle damage. The variability in T 2 changes across different muscle groups can be attributed to their different role during downhill running, with immediate T 2 elevation occurring in primary movers, followed by delayed elevation in both primary and antagonist muscle groups, presumably due to secondary damage caused by systemic processes., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background and Purpose: The physiological role of vascular β 3 -adrenoceptors is not fully understood. Recent evidence suggests cardiac β 3 -adrenoceptors are functionally effective after down-regulation of β 1 /β 2 -adrenoceptors. The functional interaction between the β 3 -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 β 3 -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 β 3 -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 β 3 -adrenoceptor agonist SR 58611A and the nonselective β-adrenoceptor agonist isoprenaline caused concentration-dependent dilation. In the presence of β 1/2 -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 β 3 -adrenoceptor antagonist L 748,337 (1 μM) inhibited vasodilation caused by β 3 -adrenoceptor agonists (in the presence of β 1/2 -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 β 3 -adrenoceptor mediated vasodilation was only evident after blockade of β 1/2 -adrenoceptors. This suggests constitutive β 1/2 -adrenoceptor activity inhibits β 3 -adrenoceptor function in the endothelium of skeletal muscle resistance arteries., (© 2021 The British Pharmacological Society.)

The tachykinin NK 2 receptor plays a key role in gastrointestinal motor function. Enteric neurons release neurokinin A (NKA), which activates NK 2 receptors on gastrointestinal smooth muscle, leading to contraction and increased motility. In patients with diarrhea-predominant irritable bowel syndrome, the NK 2 receptor antagonist ibodutant had a greater therapeutic effect in females than males. The present study aimed to determine whether gender influences the expression and activity of NK 2 receptors in human colonic smooth muscle. In vitro functional studies were performed to examine the contractile responses of colonic muscle strips to NKA and the selective NK 2 receptor agonist [Lys 5 ,MeLeu 9 ,Nle 10 ]NKA(4-10). Contractions were also measured in the presence of ibodutant to determine its antagonistic potency. The signal transduction pathways coupled to NK 2 receptor activation were investigated using second messenger inhibitors. Western blot and fluorescent immunohistochemistry were conducted to determine the protein expression and localization of NK 2 receptors. NK 2 receptor-mediated contractility was greater in females compared with males. When against NKA, ibodutant was more potent in females. NK 2 receptor expression increased with age in females, but not in males. Phospholipase C-mediated signaling was less prominent in females compared with males, whereas Ca 2+ sensitization via Rho kinase and protein kinase C appeared to be the dominant pathway in both genders. The distribution of NK 2 receptors in the human colon did not differ between the genders. Overall, gender differences exist in the expression and activity of NK 2 receptors in colonic smooth muscle. These gender distinctions should be considered in the therapeutic development of NK 2 receptor agents. SIGNIFICANCE STATEMENT: The tachykinin NK 2 receptor has been identified as a therapeutic target for the treatment of bowel and bladder dysfunctions. The present study has revealed gender-related variations in NK 2 receptor activity, signaling transduction pathways, antagonist potency, and changes in expression with age. These factors may underlie the gender differences in the treatment of diarrhea-predominant irritable bowel syndrome with NK 2 receptor antagonists. Our findings highlight that gender differences should be considered in the therapeutic development of NK 2 receptor agents., (Copyright © 2020 by The Author(s).)

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 Ca 2+ depletion ([Ca 2+ ] 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, 10 Panx1, 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. [Ca 2+ ] 0 caused a marked, but transient, elevation of extracellular ATP level in all three cell populations. CALHM1 antibody and ruthenium red inhibited [Ca 2+ ] 0 -induced ATP release from urothelial cells, but their effects on suburothelial and detrusor cells were insignificant. 10 Panx1 showed no significant inhibition of [Ca 2+ ] 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 Ca 2+ may also regulate ATP release in the porcine bladder through voltage-gated CALHM1 ion channels., (Copyright © 2017 the American Physiological Society.)