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Thomas A. Lutz - One of the best experts on this subject based on the ideXlab platform.
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Attenuation of the Anorectic effects of cholecystokinin and bombesin by the specific amylin antagonist AC 253
Physiology & behavior, 2000Co-Authors: Thomas A. Lutz, S Tschudy, Paul A. Rushing, Erwin ScharrerAbstract:Abstract Previous studies provided evidence for an interaction between the satiety effects of cholecystokinin (CCK), bombesin (BBS), and amylin. Amylin released in response to CCK (or BBS) was supposed to mediate part of CCK's (or BBS's) Anorectic effect since the amylin and calcitonin gene-related peptide (CGRP) antagonist CGRP 8–37 attenuated their Anorectic action. Due to the low specificity of CGRP 8–37 for amylin vs. CGRP binding sites, the aim of the present study was to test whether the specific amylin antagonist AC 253 also influenced the Anorectic effects of CCK and BBS. Injections took place at dark onset in 24-h food-deprived rats. At a dose that attenuated the Anorectic effect of amylin (5 μg/kg), the amylin antagonist AC 253 (500 μg/kg) significantly attenuated the Anorectic effects of CCK and BBS (0.5 μg/kg). It can therefore be concluded that amylin, rather than CGRP, mediates part of the Anorectic effects of CCK and BBS.
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lesion of the area postrema nucleus of the solitary tract ap nts attenuates the Anorectic effects of amylin and calcitonin gene related peptide cgrp in rats
Peptides, 1998Co-Authors: Thomas A. Lutz, Janine Althaus, Markus Senn, Elvira Del Prete, F Ehrensperger, E ScharrerAbstract:Abstract Lutz, T. A., M. Senn, J. Althaus, E. Del Prete, F. Ehrensperger and E. Scharrer. Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the Anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats. Peptides 19(2) 309–317, 1998.—The area postrema/nucleus of the solitary tract (AP/NTS) region plays an important role in the control of food intake since it receives peripheral satiety signals via splanchnic and vagal afferents. Due to the lack of the blood brain barrier in this region, blood borne signals can directly be monitored in the AP/NTS. Furthermore, receptors for Anorectic peptides such as amylin or calcitonin gene-related peptide (CGRP) have been found in the AP/NTS. It was therefore the aim of the present study to investigate the role of the AP/NTS region in mediating the Anorectic effects of these peptides. Thermal ablation of the AP/NTS resulted in a significant reduction of the Anorectic effects of IP injected amylin (5 μg/kg) and CGRP (5 μg/kg) in food deprived rats. The Anorectic actions of CCK and BBS were also reduced by the AP/NTS lesion which agrees with previous studies. We conclude that the AP/NTS region is an important brain site for mediating the Anorectic effects of amylin and CGRP. It remains to be clarified whether this effect is due to amylin and CGRP action on receptors within the AP/NTS region or peripheral receptors on afferent nerves projecting to the AP/NTS.
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Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats
Peptides, 1998Co-Authors: Thomas A. Lutz, R. Rossi, Janine Althaus, E. Del Prete, Erwin ScharrerAbstract:Amylin and the structurally and functionally related peptide calcitonin gene-related peptide (CGRP) have been shown to reduce food intake in rats. The aim of the present study was to compare the Anorectic potency of both peptides over a wide dose range when administered into the lateral brain ventricle (ICV). Furthermore, we also tested the influence of a lesion in the area postrema/nucleus of the solitary tract (AP/NTS) region on the Anorectic effects of amylin and CGRP after ICV administration because AP/NTS lesion has been shown to reduce the Anorectic effects of both peptides when injected intraperitoneally (IP). Amylin [1-510 pmol/rat (0.004-2 microg/rat) ICV] and CGRP [1-131 pmol/rat (0.004-0.5 microg/rat) ICV] dose-dependently reduced food intake in food-deprived rats. At a dose of 26 pmol/rat (0.1 microg/rat), amylin almost completely suppressed food intake for 1 h after injection. Amylin [EC50 = 2 pmol/rat (0.007 microg/rat)] was markedly more potent than CGRP [57 pmol/rat (0.215 microg/rat)] with regard to its Anorectic effect. A lesion in the AP/NTS region did not influence the Anorectic effects of amylin and CGRP after administration into the lateral ventricle. It is concluded that amylin is more potent than CGRP in reducing food intake after administration into the lateral brain ventricle. Receptors in the forebrain may mediate the Anorectic effects of both peptides when administered via this route.
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Inhibition of food intake in rats by the K+ channel opener cromakalim.
Pharmacology Biochemistry and Behavior, 1996Co-Authors: E. Del Prete, Thomas A. Lutz, Erwin ScharrerAbstract:We studied the effect of the K+ channel opener cromakalim, which exhibits antihypertensive properties, on food intake in rats. Intraperitoneally injected cromakalim induced a dose-dependent (0.1, 0.5, and 1.0 mg/kg body wt.) reduction in food intake, which was associated with an inhibition of gastric emptying. The Anorectic effect was not influenced by subdiaphragmatic vagotomy. Cromakalim's Anorectic effect did not appear to be due to a learned taste aversion. Therefore, an intact abdominal vagus is not a prerequisite for cromakalim's Anorectic effect.
Erwin Scharrer - One of the best experts on this subject based on the ideXlab platform.
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Attenuation of the Anorectic effects of cholecystokinin and bombesin by the specific amylin antagonist AC 253
Physiology & behavior, 2000Co-Authors: Thomas A. Lutz, S Tschudy, Paul A. Rushing, Erwin ScharrerAbstract:Abstract Previous studies provided evidence for an interaction between the satiety effects of cholecystokinin (CCK), bombesin (BBS), and amylin. Amylin released in response to CCK (or BBS) was supposed to mediate part of CCK's (or BBS's) Anorectic effect since the amylin and calcitonin gene-related peptide (CGRP) antagonist CGRP 8–37 attenuated their Anorectic action. Due to the low specificity of CGRP 8–37 for amylin vs. CGRP binding sites, the aim of the present study was to test whether the specific amylin antagonist AC 253 also influenced the Anorectic effects of CCK and BBS. Injections took place at dark onset in 24-h food-deprived rats. At a dose that attenuated the Anorectic effect of amylin (5 μg/kg), the amylin antagonist AC 253 (500 μg/kg) significantly attenuated the Anorectic effects of CCK and BBS (0.5 μg/kg). It can therefore be concluded that amylin, rather than CGRP, mediates part of the Anorectic effects of CCK and BBS.
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Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats
Peptides, 1998Co-Authors: Thomas A. Lutz, R. Rossi, Janine Althaus, E. Del Prete, Erwin ScharrerAbstract:Amylin and the structurally and functionally related peptide calcitonin gene-related peptide (CGRP) have been shown to reduce food intake in rats. The aim of the present study was to compare the Anorectic potency of both peptides over a wide dose range when administered into the lateral brain ventricle (ICV). Furthermore, we also tested the influence of a lesion in the area postrema/nucleus of the solitary tract (AP/NTS) region on the Anorectic effects of amylin and CGRP after ICV administration because AP/NTS lesion has been shown to reduce the Anorectic effects of both peptides when injected intraperitoneally (IP). Amylin [1-510 pmol/rat (0.004-2 microg/rat) ICV] and CGRP [1-131 pmol/rat (0.004-0.5 microg/rat) ICV] dose-dependently reduced food intake in food-deprived rats. At a dose of 26 pmol/rat (0.1 microg/rat), amylin almost completely suppressed food intake for 1 h after injection. Amylin [EC50 = 2 pmol/rat (0.007 microg/rat)] was markedly more potent than CGRP [57 pmol/rat (0.215 microg/rat)] with regard to its Anorectic effect. A lesion in the AP/NTS region did not influence the Anorectic effects of amylin and CGRP after administration into the lateral ventricle. It is concluded that amylin is more potent than CGRP in reducing food intake after administration into the lateral brain ventricle. Receptors in the forebrain may mediate the Anorectic effects of both peptides when administered via this route.
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Inhibition of food intake in rats by the K+ channel opener cromakalim.
Pharmacology Biochemistry and Behavior, 1996Co-Authors: E. Del Prete, Thomas A. Lutz, Erwin ScharrerAbstract:We studied the effect of the K+ channel opener cromakalim, which exhibits antihypertensive properties, on food intake in rats. Intraperitoneally injected cromakalim induced a dose-dependent (0.1, 0.5, and 1.0 mg/kg body wt.) reduction in food intake, which was associated with an inhibition of gastric emptying. The Anorectic effect was not influenced by subdiaphragmatic vagotomy. Cromakalim's Anorectic effect did not appear to be due to a learned taste aversion. Therefore, an intact abdominal vagus is not a prerequisite for cromakalim's Anorectic effect.
E Scharrer - One of the best experts on this subject based on the ideXlab platform.
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lesion of the area postrema nucleus of the solitary tract ap nts attenuates the Anorectic effects of amylin and calcitonin gene related peptide cgrp in rats
Peptides, 1998Co-Authors: Thomas A. Lutz, Janine Althaus, Markus Senn, Elvira Del Prete, F Ehrensperger, E ScharrerAbstract:Abstract Lutz, T. A., M. Senn, J. Althaus, E. Del Prete, F. Ehrensperger and E. Scharrer. Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the Anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats. Peptides 19(2) 309–317, 1998.—The area postrema/nucleus of the solitary tract (AP/NTS) region plays an important role in the control of food intake since it receives peripheral satiety signals via splanchnic and vagal afferents. Due to the lack of the blood brain barrier in this region, blood borne signals can directly be monitored in the AP/NTS. Furthermore, receptors for Anorectic peptides such as amylin or calcitonin gene-related peptide (CGRP) have been found in the AP/NTS. It was therefore the aim of the present study to investigate the role of the AP/NTS region in mediating the Anorectic effects of these peptides. Thermal ablation of the AP/NTS resulted in a significant reduction of the Anorectic effects of IP injected amylin (5 μg/kg) and CGRP (5 μg/kg) in food deprived rats. The Anorectic actions of CCK and BBS were also reduced by the AP/NTS lesion which agrees with previous studies. We conclude that the AP/NTS region is an important brain site for mediating the Anorectic effects of amylin and CGRP. It remains to be clarified whether this effect is due to amylin and CGRP action on receptors within the AP/NTS region or peripheral receptors on afferent nerves projecting to the AP/NTS.
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attenuation of the Anorectic effects of glucagon cholecystokinin and bombesin by the amylin receptor antagonist cgrp 8 37
Peptides, 1996Co-Authors: E. Del Prete, M.m. Szabady, E ScharrerAbstract:Abstract The Anorectic effect of IP injection of amylin (1 μg/kg) was abolished by simultaneous IP injection of the amylin receptor antagonist calcitonin gene-related peptide-(8–37) [CGRP(8–37), 10 μg/kg]. The IP injection of pancreatic glucagon (400 μg/kg) at dark onset also reduced food intake in 24-h food-deprived rats, and this effect was also totally blocked by coadministration of CGRP(8–37) (10 μg/kg). In another feeding paradigm with glucagon (540 μg/kg IP 3 h into the light phase in 3 h-prefed rats), however, the Anorectic effect of glucagon was not significantly antagonized by CGRP(8–37). The Anorectic effect of cholecystokinin (CCK) (0.25 μg/kg) and bombesin (BBS) (2 μg/kg) was partly neutralized by CGRP(8–37). In contrast, the Anorectic effect of vasopressin (VP) (2.5 μg/kg) was not influenced by CGRP(8–37). As glucagon has been shown previously to increase the secretion of amylin, we conclude that the Anorectic effect of peripherally administered glucagon is mediated by the release of amylin, at least under certain conditions. This may also be true for CCK and BBS, as these peptides are insulinotropic and may therefore be presumed to increase amylin release.
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reduction of food intake in rats by intraperitoneal injection of low doses of amylin
Physiology & Behavior, 1994Co-Authors: E. Del Prete, E ScharrerAbstract:Abstract The effect of amylin injected IP on food intake in rats of different age (7–9 weeks, 3 months, 15–18 months) was investigated. The possible site of amylin action was investigated using vagotomized rats. Lastly, the influence of food composition on amylin's effect was investigated. In 12-h food-deprived old rats, food intake was decreased significantly by amylin (1–10 μg/kg) when injected at the beginning of the dark phase. Although the Anorectic effect of amylin occurred somewhat earlier at 10 μg/kg, no clear dose-response relationship was observed. The Anorectic effect was most marked in the first 2 h after amylin injection and was compensated over 24 h. Amylin (1 and 5 μg/kg) did not reduce food intake in undeprived old rats. In young rats, amylin (0.1–1 μg/kg) dose-dependently reduced food intake if rats were food-deprived for 24 h, but not when deprived for 12 h. Dissection of the common hepatic vagus branch did not block the Anorectic effect of amylin (age of rats: 3 months). The effect tended to last longer in vagotomized rats. The Anorectic effect of amylin did not depend on the presence of carbohydrates in the diet. Water intake was not affected by amylin in water-deprived rats. In conclusion, the Anorectic effect of amylin was observed at much lower doses (minimal effective dose: 0.5 μg/kg) than reported before. These doses are similar to Anorectic doses of cholecystokinin, a physiological peripheral satiety agent.
Neil E. Rowland - One of the best experts on this subject based on the ideXlab platform.
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effect of serotonergic Anorectics on food intake and induction of fos in brain of mice with disruption of melanocortin 3 and or 4 receptors
Pharmacology Biochemistry and Behavior, 2010Co-Authors: Neil E. Rowland, Kaihan Fakhar, Kimberly L Robertson, Carrie HaskellluevanoAbstract:Previous studies have indicated that type 3 or 4 melanocortin receptors (MCR) are downstream of the critical Anorectic action of drugs that stimulate 5-HT2C receptors. To characterize further the receptor types involved, we have studied the effect of serotonergic Anorectics in mice with genomic disruption of either MC3R or MC4R, or their combined knockout. In a first experiment, we showed that wild type (WT) and MC4R−/− mice showed comparable inhibition of food intake following acute treatment with dexnorfenfluramine. In a second experiment using WAY-161503, a 5-HT receptor full agonist with selectivity for 2B and 2C subtypes, we found that MC4R−/− responded comparably to WT, while MC3R−/− had reduced sensitivity. Double receptor knockout (DKO) mice responded comparably to WT and MC4R−/−. Surprisingly, brain Fos-ir was not strongly induced in any brain region by WAY-16103 with the exception of the paraventricular nucleus of DKO. These data suggest that MC3Rs may be involved in the response to serotonergic Anorectic agents, and more generally in control of food intake.
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Anorectic efficacy of the fenfluramine phentermine combination in rats additivity or synergy
European Journal of Pharmacology, 1999Co-Authors: Jonathan D Roth, Neil E. RowlandAbstract:Fenfluramine + phentermine was a widely used combination for weight loss. Fenfluramine and phentermine are believed to act via serotonin and catecholamines, respectively. To what extent these drugs interact has not been well-established. We compared the Anorectic efficacy of a range of doses of the combination (using dexfenfluramine instead of fenfluramine) relative to a range of doses of the individual drugs in 90 min sweetened milk intake tests in deprived and nondeprived rats. Results were plotted on isobolograms to determine whether the Anorectic effects of the combination were either additive or synergistic. Collectively, the isobolographic analysis revealed that: (1) under acute conditions, dexfenfluramine and phentermine interact for the most part in a synergistic manner, and (2) with the exception of phentermine alone, deprivation state at time of testing did not alter the efficacy of the Anorectics. These findings suggest that combined drug treatment for obesity is a theoretical approach that merits further investigation.
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Anorectic efficacy of the fenfluramine/phentermine combination in rats : additivity or synergy?
European Journal of Pharmacology, 1999Co-Authors: Jonathan D Roth, Neil E. RowlandAbstract:Fenfluramine + phentermine was a widely used combination for weight loss. Fenfluramine and phentermine are believed to act via serotonin and catecholamines, respectively. To what extent these drugs interact has not been well-established. We compared the Anorectic efficacy of a range of doses of the combination (using dexfenfluramine instead of fenfluramine) relative to a range of doses of the individual drugs in 90 min sweetened milk intake tests in deprived and nondeprived rats. Results were plotted on isobolograms to determine whether the Anorectic effects of the combination were either additive or synergistic. Collectively, the isobolographic analysis revealed that: (1) under acute conditions, dexfenfluramine and phentermine interact for the most part in a synergistic manner, and (2) with the exception of phentermine alone, deprivation state at time of testing did not alter the efficacy of the Anorectics. These findings suggest that combined drug treatment for obesity is a theoretical approach that merits further investigation.
E. Del Prete - One of the best experts on this subject based on the ideXlab platform.
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Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats
Peptides, 1998Co-Authors: Thomas A. Lutz, R. Rossi, Janine Althaus, E. Del Prete, Erwin ScharrerAbstract:Amylin and the structurally and functionally related peptide calcitonin gene-related peptide (CGRP) have been shown to reduce food intake in rats. The aim of the present study was to compare the Anorectic potency of both peptides over a wide dose range when administered into the lateral brain ventricle (ICV). Furthermore, we also tested the influence of a lesion in the area postrema/nucleus of the solitary tract (AP/NTS) region on the Anorectic effects of amylin and CGRP after ICV administration because AP/NTS lesion has been shown to reduce the Anorectic effects of both peptides when injected intraperitoneally (IP). Amylin [1-510 pmol/rat (0.004-2 microg/rat) ICV] and CGRP [1-131 pmol/rat (0.004-0.5 microg/rat) ICV] dose-dependently reduced food intake in food-deprived rats. At a dose of 26 pmol/rat (0.1 microg/rat), amylin almost completely suppressed food intake for 1 h after injection. Amylin [EC50 = 2 pmol/rat (0.007 microg/rat)] was markedly more potent than CGRP [57 pmol/rat (0.215 microg/rat)] with regard to its Anorectic effect. A lesion in the AP/NTS region did not influence the Anorectic effects of amylin and CGRP after administration into the lateral ventricle. It is concluded that amylin is more potent than CGRP in reducing food intake after administration into the lateral brain ventricle. Receptors in the forebrain may mediate the Anorectic effects of both peptides when administered via this route.
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attenuation of the Anorectic effects of glucagon cholecystokinin and bombesin by the amylin receptor antagonist cgrp 8 37
Peptides, 1996Co-Authors: E. Del Prete, M.m. Szabady, E ScharrerAbstract:Abstract The Anorectic effect of IP injection of amylin (1 μg/kg) was abolished by simultaneous IP injection of the amylin receptor antagonist calcitonin gene-related peptide-(8–37) [CGRP(8–37), 10 μg/kg]. The IP injection of pancreatic glucagon (400 μg/kg) at dark onset also reduced food intake in 24-h food-deprived rats, and this effect was also totally blocked by coadministration of CGRP(8–37) (10 μg/kg). In another feeding paradigm with glucagon (540 μg/kg IP 3 h into the light phase in 3 h-prefed rats), however, the Anorectic effect of glucagon was not significantly antagonized by CGRP(8–37). The Anorectic effect of cholecystokinin (CCK) (0.25 μg/kg) and bombesin (BBS) (2 μg/kg) was partly neutralized by CGRP(8–37). In contrast, the Anorectic effect of vasopressin (VP) (2.5 μg/kg) was not influenced by CGRP(8–37). As glucagon has been shown previously to increase the secretion of amylin, we conclude that the Anorectic effect of peripherally administered glucagon is mediated by the release of amylin, at least under certain conditions. This may also be true for CCK and BBS, as these peptides are insulinotropic and may therefore be presumed to increase amylin release.
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Inhibition of food intake in rats by the K+ channel opener cromakalim.
Pharmacology Biochemistry and Behavior, 1996Co-Authors: E. Del Prete, Thomas A. Lutz, Erwin ScharrerAbstract:We studied the effect of the K+ channel opener cromakalim, which exhibits antihypertensive properties, on food intake in rats. Intraperitoneally injected cromakalim induced a dose-dependent (0.1, 0.5, and 1.0 mg/kg body wt.) reduction in food intake, which was associated with an inhibition of gastric emptying. The Anorectic effect was not influenced by subdiaphragmatic vagotomy. Cromakalim's Anorectic effect did not appear to be due to a learned taste aversion. Therefore, an intact abdominal vagus is not a prerequisite for cromakalim's Anorectic effect.
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Circadian Anorectic effects of peripherally administered amylin in rats
Zeitschrift fur Ernahrungswissenschaft, 1995Co-Authors: E. Del Prete, M.m. SzabadyAbstract:The pancreatic peptide amylin (1 µg/kg) injected intraperitoneally reduced cumulative food intake for up to 4 h in food-deprived (24 h) and non-deprived rats at various times of the day, i.e., at dark onset, in the middle of the dark phase, and at light onset. At none of these times did subdiaphragmatic vagotomy abolish the Anorectic effect of amylin. Rather, vagotomy enhanced, by unknown mechanisms, amylin's Anorectic effect in food-deprived rats at light onset and in the middle of the dark phase. In contrast to previous studies with older rats, amylin's Anorectic effect was also observed when injected into nondeprived rats. The findings of the present study extend previous reports in that amylin's Anorectic effect, not being abolished by abdominal vagotomy after intraperitoneal injection, can be elicited at different times of the day.
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reduction of food intake in rats by intraperitoneal injection of low doses of amylin
Physiology & Behavior, 1994Co-Authors: E. Del Prete, E ScharrerAbstract:Abstract The effect of amylin injected IP on food intake in rats of different age (7–9 weeks, 3 months, 15–18 months) was investigated. The possible site of amylin action was investigated using vagotomized rats. Lastly, the influence of food composition on amylin's effect was investigated. In 12-h food-deprived old rats, food intake was decreased significantly by amylin (1–10 μg/kg) when injected at the beginning of the dark phase. Although the Anorectic effect of amylin occurred somewhat earlier at 10 μg/kg, no clear dose-response relationship was observed. The Anorectic effect was most marked in the first 2 h after amylin injection and was compensated over 24 h. Amylin (1 and 5 μg/kg) did not reduce food intake in undeprived old rats. In young rats, amylin (0.1–1 μg/kg) dose-dependently reduced food intake if rats were food-deprived for 24 h, but not when deprived for 12 h. Dissection of the common hepatic vagus branch did not block the Anorectic effect of amylin (age of rats: 3 months). The effect tended to last longer in vagotomized rats. The Anorectic effect of amylin did not depend on the presence of carbohydrates in the diet. Water intake was not affected by amylin in water-deprived rats. In conclusion, the Anorectic effect of amylin was observed at much lower doses (minimal effective dose: 0.5 μg/kg) than reported before. These doses are similar to Anorectic doses of cholecystokinin, a physiological peripheral satiety agent.