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Romina Nassini - One of the best experts on this subject based on the ideXlab platform.
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ureteral relaxation through Calcitonin gene related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.
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Ureteral relaxation through Calcitonin gene‐related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.
Peter J. Goadsby - One of the best experts on this subject based on the ideXlab platform.
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Rimegepant, an Oral Calcitonin Gene–Related Peptide Receptor Antagonist, for Migraine
The New England Journal of Medicine, 2019Co-Authors: Richard B. Lipton, Robert Croop, E Stock, David A Stock, Beth A Morris, Marianne Frost, Gene M Dubowchik, Charles M Conway, Vladimir Coric, Peter J. GoadsbyAbstract:Abstract Background Calcitonin gene–related Peptide receptor has been implicated in the pathogenesis of migraine. Rimegepant is an orally administered, small-molecule, Calcitonin gene–related pepti...
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rimegepant an oral Calcitonin gene related Peptide receptor antagonist for migraine
The New England Journal of Medicine, 2019Co-Authors: Richard B. Lipton, Robert Croop, E Stock, David A Stock, Beth A Morris, Marianne Frost, Gene M Dubowchik, Charles M Conway, Vladimir Coric, Peter J. GoadsbyAbstract:Abstract Background Calcitonin gene–related Peptide receptor has been implicated in the pathogenesis of migraine. Rimegepant is an orally administered, small-molecule, Calcitonin gene–related pepti...
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Modulation of nocioceptive transmission with Calcitonin Gene-Related Peptide receptor antagonists in the thalamus
Brain, 2010Co-Authors: O. Summ, Annabelle R Charbit, Anna P Andreou, Peter J. GoadsbyAbstract:Calcitonin Gene-Related Peptide receptor antagonists are effective acute migraine treatments without the vascular contraindications associated with triptans. While it has been demonstrated that Calcitonin Gene-Related Peptide receptor antagonists act in the central nervous system, their effects in preclinical migraine models have been investigated in only the trigeminocervical complex. Migraine is a complex neurological disorder; sites in the brainstem and forebrain are clearly involved in its expression. We have performed electrophysiological recordings in thalamic neurons of rats responding to nocioceptive trigeminovascular inputs and tested the effect of olcegepant, a Calcitonin Gene-Related Peptide receptor antagonist (1 mg/kg, intravenously), on cell firing. We further tested the effect of microiontophoresed Calcitonin Gene-Related Peptide and the receptor antagonists Calcitonin Gene-Related Peptide 8-37 and olcegepant on thalamic cell firing, elicited by stimulation of the superior sagittal sinus or by microiontophoretic application of L -glutamate. Additionally, we used immunofluorescent staining to demonstrate the presence of functional Calcitonin Gene-Related Peptide receptors in the ventroposteromedial thalamic nucleus by specifically co-staining for the Calcitonin Gene-Related Peptide receptor subunits Calcitonin receptor-like receptor and receptor activity modifying protein 1. Intravenously administered olcegepant significantly inhibited cell firing evoked by stimulation of the superior sagittal sinus as well as the background activity. Microiontophoresis of Calcitonin Gene-Related Peptide 8-37 also showed a significant inhibition of L -glutamate-evoked cell firing and firing evoked by stimulation of the superior sagittal sinus. Immunofluorescent staining confirmed the presence of the components of a functional Calcitonin Gene-Related Peptide receptor, the Calcitonin receptor-like receptor and the receptor activity modifying protein 1, within the area of the ventroposteromedial thalamic nucleus. This is the first report on the efficacy of Calcitonin Gene-Related Peptide receptor antagonists at the level of third-order neurons in the migraine pathway, showing that the central effects of Calcitonin Gene-Related Peptide receptor antagonists extend beyond the trigeminocervical complex at least to the sensory thalamus.
Serena Materazzi - One of the best experts on this subject based on the ideXlab platform.
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ureteral relaxation through Calcitonin gene related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.
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Ureteral relaxation through Calcitonin gene‐related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.
Gaetano De Siena - One of the best experts on this subject based on the ideXlab platform.
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ureteral relaxation through Calcitonin gene related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.
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Ureteral relaxation through Calcitonin gene‐related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.
Daiana Minocci - One of the best experts on this subject based on the ideXlab platform.
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ureteral relaxation through Calcitonin gene related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.
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Ureteral relaxation through Calcitonin gene‐related Peptide release from sensory nerve terminals by hypotonic solution
International Journal of Urology, 2015Co-Authors: Serena Materazzi, Daiana Minocci, Gaetano De Siena, Silvia Benemei, Romina NassiniAbstract:Objectives To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of Calcitonin Gene-Related Peptide from intramural sensory nerve endings. Methods Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A-induced phasic contractions of isolated rat ureters was evaluated by organ bath studies. Results A 7-day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released Calcitonin Gene-Related Peptide-like immunoreactivity from slices of rat ureter. This response was abated in a calcium-free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A-evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the Calcitonin Gene-Related Peptide receptor antagonist, Calcitonin Gene-Related Peptide8-37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and Calcitonin Gene-Related Peptide-dependent relaxation. Conclusion Present data show that hypotonic solution evokes Calcitonin Gene-Related Peptide release from capsaicin-sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential-dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.