The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Petter Hedlund - One of the best experts on this subject based on the ideXlab platform.
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the transient receptor potential a1 ion channel trpa1 modifies in vivo autonomous Ureter Peristalsis in rats
Neurourology and Urodynamics, 2021Co-Authors: Philipp Weinhold, Luca Villa, Frank Strittmatter, Christian Gratzke, Christian G Stief, Fabio Castiglione, Francesco Montorsi, Petter HedlundAbstract:Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat Ureter and to assess if TRPA1-active compounds modulate Ureter function. Methods: The expression of TRPA1 in rat Ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right Ureter of 50 rats. Ureter Peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results: TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the Ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the Ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of Ureter Peristalsis versus baseline in vehicle-treated rats (p < 0.001) but not in HC030031-treated rats. CA (p < 0.001) and NaHS (p < 0.001) decreased Ureter Peristalsis. This was counteracted by HC030031 (p < 0.05 and p < 0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the Ureter. Functional data indicate that TRPA1-mediated signals regulate Ureter Peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in Ureter pathologies involving urothelial damage. (Less)
Fabio Castiglione - One of the best experts on this subject based on the ideXlab platform.
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the transient receptor potential a1 ion channel trpa1 modifies in vivo autonomous Ureter Peristalsis in rats
Neurourology and Urodynamics, 2021Co-Authors: Philipp Weinhold, Luca Villa, Frank Strittmatter, Christian Gratzke, Christian G Stief, Fabio Castiglione, Francesco Montorsi, Petter HedlundAbstract:Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat Ureter and to assess if TRPA1-active compounds modulate Ureter function. Methods: The expression of TRPA1 in rat Ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right Ureter of 50 rats. Ureter Peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results: TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the Ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the Ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of Ureter Peristalsis versus baseline in vehicle-treated rats (p < 0.001) but not in HC030031-treated rats. CA (p < 0.001) and NaHS (p < 0.001) decreased Ureter Peristalsis. This was counteracted by HC030031 (p < 0.05 and p < 0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the Ureter. Functional data indicate that TRPA1-mediated signals regulate Ureter Peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in Ureter pathologies involving urothelial damage. (Less)
Philipp Weinhold - One of the best experts on this subject based on the ideXlab platform.
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the transient receptor potential a1 ion channel trpa1 modifies in vivo autonomous Ureter Peristalsis in rats
Neurourology and Urodynamics, 2021Co-Authors: Philipp Weinhold, Luca Villa, Frank Strittmatter, Christian Gratzke, Christian G Stief, Fabio Castiglione, Francesco Montorsi, Petter HedlundAbstract:Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat Ureter and to assess if TRPA1-active compounds modulate Ureter function. Methods: The expression of TRPA1 in rat Ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right Ureter of 50 rats. Ureter Peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results: TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the Ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the Ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of Ureter Peristalsis versus baseline in vehicle-treated rats (p < 0.001) but not in HC030031-treated rats. CA (p < 0.001) and NaHS (p < 0.001) decreased Ureter Peristalsis. This was counteracted by HC030031 (p < 0.05 and p < 0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the Ureter. Functional data indicate that TRPA1-mediated signals regulate Ureter Peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in Ureter pathologies involving urothelial damage. (Less)
Hansjorg Danuser - One of the best experts on this subject based on the ideXlab platform.
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effects of ketanserin and doi on spontaneous and 5 ht evoked Peristalsis of the pig Ureter in vivo
British Journal of Pharmacology, 2002Co-Authors: Daniela S Hauser, Meike Mevissen, Ruth Weiss, Christopher J Portier, Gunter Scholtysik, Urs E Studer, Hansjorg DanuserAbstract:The influence of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on the Ureter motility was investigated in vivo on intact Ureters of anaesthetized pigs. Drugs were administered intravenously or topically. 5-HT induced a dose-dependent increase in the frequency of Ureter contractions in anaesthetized pigs when given intravenously (0.0001 – 1 mg kg−1; ED50 0.066 mg kg−1) or topically (0.001 – 1 mg ml−1; EC50 0.043 mg ml−1). Significant increases in heart rate and blood pressure were observed when the drug was given intravenously but not topically. The 5-HT2A agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) increased the frequency of Ureteral contractions in a dose-dependent manner (1 – 300 μg kg−1 i.v.). Calculation of ED50 indicated this compound to be about 1.5 times more potent with an efficacy of 23% compared to 5-HT. The 5-HT2A/2C antagonist, ketanserin (0.5 mg kg−1) and the 5-HT2C antagonist, methysergide (1 mg kg−1) antagonized the 5-HT-induced Ureter Peristalsis when given intravenously. Contraction amplitude, blood pressure and heart rate were not affected by the antagonists. Intravenous (0.0001 – 1 mg kg−1) and topical (0.0001 – 1 μg ml−1) ketanserin significantly decreased the frequency of spontaneous Ureteral contractions to about 30% of controls, which could be partly reversed by 5-HT (0.3 mg kg−1 i.v.). The contraction amplitude, contractions of the contralateral, saline perfused Ureter, heart rate and mean arterial blood pressure were not affected. Thus, contractility of porcine Ureter is mediated by 5-HT2 receptors. Their antagonists ketanserin and methysergide seem to be promising drugs for treatment of acute Ureteric colic or in preparing the Ureter for Ureteroscopy. Keywords: Ureteral Peristalsis, pig Ureter, receptors, 5-hydroxytryptamine, DOI, ketanserin, 5-HT2A receptor antagonists Introduction So far a wide variety of 5-hydroxytryptamine (5-HT) receptors and their subtypes have been characterized in different tissues and the nomenclature for 5-HT receptors has undergone a considerable evolution during the past ten years, principally in response to a rapidly expanding database of information concerning structure and function at the molecular level. According to the current opinion there are seven main classes of 5-HT receptors and some of these groups comprise multiple receptor subtypes: 5-HT1 (1A, 1B, 1D, 1e, 1f), 5-HT2 (2A, 2B, 2C), 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7 (Martin, 1998). It should be noted that receptors previously labelled 5-HT1-like are a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7 receptors (Saxena et al., 1998). 5-HT is well known to induce Ureteral contractions in isolated Ureter preparations from different species (Hertle & Nawrath, 1986; Dodel et al., 1996; Kuwahara, 1983; Long & Nergardh, 1978; Gidener et al., 1995; 1999; Benzi et al., 1970; Iselin et al., 1997) and in vivo (Abrahams & Pickford, 1956; Catacutan-Labay et al., 1966; Boatman et al., 1967). Nevertheless it is still unclear which 5-HT receptor subtype is responsible for the stimulating effect and whether 5-HT is physiologically involved in Ureter motility. Long & Nergardh (1978) demonstrated that 5-HT evoked a concentration-dependent increase of contractions in isolated human Ureter strips which could be blocked by methysergide, a mixed 5-HT1/2A/2C receptor antagonist. In accordance with these results other authors reported an inhibition of 5-HT-evoked contractions on human Ureter in vitro by methysergide and the 5-HT2A/2C receptor antagonist ketanserin that also interacts with α-adrenergic and histaminergic receptors (Gidener et al., 1995; Leysen et al., 1981). However, the effect of 5-HT was unaltered after blocking 5-HT3 and 5-HT4 receptors and cholinergic muscarinic receptors (Gidener et al., 1995). In a more recent work of Gidener et al. (1999), 5-HT-evoked contractions on human Ureter strips could be antagonized by ketanserin. In addition, combined administration of the 5-HT4 receptor antagonist DAU 6285 and the 5-HT3 receptor antagonist ondansetron caused a rightward shift of the cumulative concentration-response curve of 5-HT. Given individually, the 5-HT receptor antagonists methiothepin with higher affinity to 5-HT7 than to 5-HT1A, ondansetron and DAU 6285 were unable to antagonise the contractions evoked by 5-HT. In a recently published work 8-hydroxy-2-(n-dipropylamino)tetralin HBr (8-OH-DPAT; 5-HT1A/7 receptor agonists), sumatriptan (5-HT1B/1D receptor agonist), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 5-HT2A/2C receptor agonist), 2-methyl 5-HT (5-HT3 receptor agonist) and renzapride (5-HT4 receptor agonist) all failed to induce a contractile response, whereas 5-carboxyaminotryptamine maleate (5-CT; 5-HT1A/1B receptor agonist) evoked contractions on isolated human Ureter specimens (Gidener et al., 1999). In vivo studies on the Ureteral effects of 5-HT were reported about 40 years ago, and information is available from in vitro studies, including human tissues using subtype specific 5-HT receptor agonists and antagonists. However, the later results were not yet confirmed in vivo. The purpose of this study was to investigate the effects of 5-HT and the 5-HT2A/2C receptor agonist DOI and the 5-HT2 antagonists ketanserin and methysergide on porcine Ureter motility in vivo, a model in which the regulation of motility by adrenoceptors has been investigated extensively (Danuser et al., 2001).
Christian G Stief - One of the best experts on this subject based on the ideXlab platform.
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the transient receptor potential a1 ion channel trpa1 modifies in vivo autonomous Ureter Peristalsis in rats
Neurourology and Urodynamics, 2021Co-Authors: Philipp Weinhold, Luca Villa, Frank Strittmatter, Christian Gratzke, Christian G Stief, Fabio Castiglione, Francesco Montorsi, Petter HedlundAbstract:Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat Ureter and to assess if TRPA1-active compounds modulate Ureter function. Methods: The expression of TRPA1 in rat Ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right Ureter of 50 rats. Ureter Peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results: TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the Ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the Ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of Ureter Peristalsis versus baseline in vehicle-treated rats (p < 0.001) but not in HC030031-treated rats. CA (p < 0.001) and NaHS (p < 0.001) decreased Ureter Peristalsis. This was counteracted by HC030031 (p < 0.05 and p < 0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the Ureter. Functional data indicate that TRPA1-mediated signals regulate Ureter Peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in Ureter pathologies involving urothelial damage. (Less)
