scholarly journals Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake

2005 ◽  
Vol 288 (6) ◽  
pp. R1499-R1508 ◽  
Author(s):  
David M. Savastano ◽  
Melissa Carelle ◽  
Mihai Covasa
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Dose Response ◽  
Sucrose Intake ◽  
Hydrolytic Product ◽  
Intraduodenal Infusion ◽  
Time Points ◽  
Glucosidase Inhibitor ◽  
Type 3 ◽  
Response Testing

Ondansetron, a selective serotonin-type 3 (5-HT3) receptor antagonist, was used to test the hypothesis that duodenal infusion of isosmotic solutions of Polycose or its hydrolytic product glucose suppressed intake through 5-HT3 receptors. Polycose suppressed sucrose intake across both concentrations infused (132 mM, 7.6 ± 0.6 ml; 263 mM, 2.3 ± 0.5 ml), compared with intake under control conditions (12.6 ± 0.3 ml, P <0.001). Pretreatment with 1.0 mg/kg ondansetron attenuated reduction of sucrose intake induced only by the highest concentration of Polycose (4.6 ± 0.8 ml, P = 0.004). Dose-response testing revealed that suppression of food intake by 263 mM Polycose was equally attenuated by ondansetron administered at 1.0, 2.0, and 5.0 mg/kg but not when given at 0.125, 0.25, and 0.5 mg/kg. Acarbose, an α-glucosidase inhibitor, attenuated Polycose-induced suppression of food intake, and pretreatment with 1.0 mg/kg ondansetron had no further effect. Suppression of intake after 990 mM glucose but not mannitol infusion was attenuated by pretreatment with 1.0 mg/kg ondansetron. The competitive SGLT1 inhibitor, phloridzin, had no effect on 60-min 990 mM glucose-induced suppression of intake or the ability of ondansetron to attenuate this suppression of intake. Conversely, glucose-induced suppression of intake was attenuated by phloridzin at earlier time points and further attenuated when rats were pretreated with 1.0 mg/kg ondansetron. Ondansetron administration alone had no effect on intake at any dose tested. We conclude that 5-HT3 receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a posthydrolytic, preabsorptive mechanism.

Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain

2007 ◽  
Vol 292 (3) ◽  
pp. R1063-R1070 ◽  
Author(s):  
David M. Savastano ◽  
Matthew R. Hayes ◽  
Mihai Covasa
Keyword(s):  
Small Intestine ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Sucrose Solution ◽  
Receptor Activation ◽  
Sucrose Intake ◽  
Neuronal Responses ◽  
Vehicle Injection ◽  
Dorsal Hindbrain ◽  
Type 3

Several gastrointestinal stimuli, including some intestinal nutrients, have been shown to exert their satiating effect via activation of serotonin type-3 (5-HT3) receptors. The presence of lipids in the small intestine potently suppresses food intake; however, whether 5-HT3 receptors play a role in this response has not been directly examined. Therefore, using the selective 5-HT3 receptor antagonist ondansetron, we tested the hypothesis that duodenal infusion of lipid suppresses intake of both sucrose solution and chow through 5-HT3 receptor activation. Rats duodenally infused with 72 and 130 mM Intralipid suppressed 1-h 15% sucrose intake by 33 and 67%, respectively. Suppression of sucrose intake by 72 mM Intralipid was significantly attenuated by ondansetron at all doses tested (0.5, 1.0, 2.0, and 5.0 mg/kg ip), whereas the lowest effective dose of ondansetron to attenuate suppression of intake by 130 mM Intralipid was 1.0 mg/kg. Furthermore, infusion of 130 mM Intralipid suppressed 1- and 4-h chow intake by 35 and 20%, respectively. Ondansetron administered as low as 0.5 mg/kg significantly attenuated 1-h Intralipid-induced suppression of chow intake and completely reversed the suppression by 4 h. Administration of ondansetron alone did not alter sucrose or chow intake compared with vehicle injection at any time. Finally, to test whether Intralipid-induced neuronal activation of the dorsal vagal complex is mediated by 5-HT3 receptors, Fos-like immunoreactivity (Fos-LI) was quantified in ondansetron-pretreated rats following intestinal lipid infusion. Ondansetron (1 mg/kg) significantly attenuated duodenal intralipid-induced Fos-LI in the dorsal hindbrain. These data support the hypothesis that 5-HT3 receptors mediate both satiation, as well as hindbrain neuronal responses evoked by intestinal lipids.

scholarly journals Hindbrain administration of NMDA receptor antagonist AP-5 increases food intake in the rat

2006 ◽  
Vol 290 (3) ◽  
pp. R642-R651 ◽  
Author(s):  
Chun-Yi Hung ◽  
M. Covasa ◽  
R. C. Ritter ◽  
G. A. Burns
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Intraperitoneal Injection ◽  
Sucrose Solution ◽  
Nmda Receptor Antagonist ◽  
Saline Control ◽  
Sucrose Intake ◽  
Mk 801

Hindbrain administration of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) channel blocker, increases meal size, suggesting NMDA receptors in this location participate in control of food intake. However, dizocilpine (MK-801) reportedly antagonizes some non-NMDA ion channels. Therefore, to further assess hindbrain NMDA receptor participation in food intake control, we measured deprivation-induced intakes of 15% sucrose solution or rat chow after intraperitoneal injection of either saline vehicle or d(-)-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, to the fourth ventricular, or nucleus of the solitary tract (NTS). Intraperitoneal injection of AP5 (0.05, 0.1, 1.0, 3.0, and 5.0 mg/kg) did not alter 30-min sucrose intake at any dose (10.7 ± 0.4 ml, saline control) (11.0 ± 0.8, 11.2 ± 1.0, 11.2 ± 1.0, 13.1 ± 2.2, and 11.0 ± 1.9 ml, AP5 doses, respectively). Fourth ventricular administration of both 0.2 μg (16.7 ± 0.6 ml) and 0.4 μg (14.9 ± 0.5 ml) but not 0.1 and 0.6 μg of AP5 significantly increased 60-min sucrose intake compared with saline (11.2 ± 0.4 ml). Twenty-four hour chow intake also was increased compared with saline (AP5: 31.5 ± 0.1 g vs. saline: 27.1 ± 0.6 g). Furthermore, rats did not increase intake of 0.2% saccharin after fourth ventricular AP5 administration (AP5: 9.8 ± 0.7ml, vs. saline: 10.5 ± 0.5ml). Finally, NTS AP5 (20 ng/30 nl) significantly increased 30- (AP5: 17.2 ± 0.7 ml vs. saline: 14.6 ± 1.7 ml), and 60-min (AP5: 19.4 ± 0.6 ml vs. saline: 15.5 ± 1.4 ml) sucrose intake, as well as 24-h chow intake (AP5: 31.6 ± 0.3 g vs. saline: 26.1 ± 1.2 g). These results support the hypothesis that hindbrain NMDA receptors participate in control of food intake and suggest that this participation also may contribute to control of body weight over a 24-h period.

Cholinergic neurotransmission participates in increased food intake induced by NMDA receptor blockade

2003 ◽  
Vol 285 (3) ◽  
pp. R641-R648 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter ◽  
Gilbert A. Burns
Keyword(s):  
Gastric Emptying ◽  
Nmda Receptor ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Motor Neurons ◽  
Nmda Receptor Antagonist ◽  
Sucrose Intake ◽  
Cholinergic Mechanism ◽  
Mk 801 ◽  
Cholinergic Tone

MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, enhances gastric emptying while increasing food intake. Although our previously reported results implicate the vagus in MK-801's effect on feeding, it is not clear whether vagal motor fibers participate in the feeding response. Control of gastric emptying is exerted, in part, by cholinergic vagal motor neurons. Therefore, we examined the ability of MK-801 to increase meal size in the presence or absence of the muscarinic receptor antagonist atropine methyl nitrate. Both central and systemic administration of MK-801 significantly increased intake of 15% sucrose. Intraperitoneal injection of atropine abolished MK-801-induced increase in sucrose intake, whereas administration into the fourth ventricle had no effect. To determine whether augmentation of cholinergic tone produces an enhancement of food intake in the absence of MK-801, we tested the ability of cisapride, a gastric prokinetic agent that promotes acetylcholine release through an action on presynaptic serotonin (5-HT4) receptors, to increase sucrose consumption. Cisapride (500 μg/kg ip) induced a small but significant increase in 15% sucrose intake (15.5 ± 0.5 ml) compared with NaCl (13.0 ± 0.6 ml). Furthermore, when MK-801 (100 μg/kg ip) was given in combination with cisapride, intake was significantly higher (19.8 ± 0.9 ml) than following either agent given alone. Pretreatment with atropine abolished the cisapride-induced increase in intake (12.1 ± 0.9 ml) as well as the increased intake induced by combining MK-801 and cisapride. These results suggest that blockade of NMDA-gated ion channels in the hindbrain increases food intake, in part, via a peripheral muscarinic cholinergic mechanism.

Reduction of food intake by intestinal macronutrient infusion is not reversed by NMDA receptor blockade

2000 ◽  
Vol 278 (2) ◽  
pp. R345-R351 ◽  
Author(s):  
M. Covasa ◽  
R. C. Ritter ◽  
G. A. Burns
Keyword(s):  
Oleic Acid ◽  
Nmda Receptor ◽  
Food Intake ◽  
Intraperitoneal Injection ◽  
Receptor Blockade ◽  
Sucrose Intake ◽  
Sham Feeding ◽  
Mk 801 ◽  
Intraduodenal Infusion ◽  
Nmda Receptor Blockade

Rats increase their intake of food, but not water, after intraperitoneal injection of MK-801, a noncompetitive antagonist of N-methyl-d-aspartate-activated ion channels. We hypothesized that MK-801 might enhance intake by interfering with intestinal chemosensory signals. To test this hypothesis, we examined the effect of the antagonist on 15% sucrose intake after an intraduodenal infusion of maltotriose, oleic acid, or phenylalanine in both real- and sham-feeding paradigms. MK-801 (100 μg/kg) significantly increased sucrose intake regardless of the composition of the infusate during real feeding. Furthermore, MK-801 had no effect on reduction of sucrose intake by intestinal nutrient infusions in sham-feeding rats. These results indicate that MK-801 does not increase meal size and duration by interfering with signals activated by intestinal macronutrients.

Serotonin type-3 receptors mediate cholecystokinin-induced satiation through gastric distension

2006 ◽  
Vol 291 (1) ◽  
pp. R115-R123 ◽  
Author(s):  
Matthew R. Hayes ◽  
Fiona M. Chory ◽  
Claire A. Gallagher ◽  
Mihai Covasa
Keyword(s):  
Food Intake ◽  
Gastric Distension ◽  
Sucrose Intake ◽  
Gastric Balloon ◽  
Sham Feeding ◽  
Balloon Distension ◽  
Type 3

We have previously shown that serotonin type-3 (5-HT3) receptors mediate cholecystokinin (CCK)-induced satiation and that this effect is dependent on postoropharyngeal feedback. However, the independent contributions of gastric and intestinal feedback in 5-HT3 receptor mediation of suppression of food intake by CCK have not been determined. Using a sham-feeding preparation combined with intraduodenal sucrose infusion, we show that blockade of 5-HT3 receptors by ondansetron (1 mg/kg ip) had no effect on suppression of sham feeding by intraduodenal 15% sucrose infusion (4 ml/10 min), CCK (2 μg/kg ip) administration, or the combination of the two treatments. In separate experiments consisting of either sham-feeding rats that received gastric distension with the use of a balloon or real-feeding rats whose stomachs were distended using gastric loads of saline after the occlusion of the pylorus, we tested the hypothesis that gastric feedback signals are necessary for activation of 5-HT3 receptors. Ondansetron significantly attenuated suppression of sham sucrose intake after a 10-ml gastric balloon distension (30.5 ± 2.2 vs. 20.2 ± 2.2 ml, respectively) and gastric distension combined with CCK (21.9 ± 1.4 vs. 12.0 ± 1.7 ml, respectively). When intestinal feedback was eliminated in a real-feeding paradigm by closing the pylorus using a cuff preparation, ondansetron attenuated suppression of sucrose intake produced by a 10-ml saline gastric load (6.8 ± 0.7 vs. 4.2 ± 0.4 ml, respectively). Finally, when CCK (1 μg/kg) was administered in combination with a 5-ml saline gastric load in a real-feeding preparation, ondansetron significantly attenuated suppression of sucrose intake by CCK (9.0 ± 0.9 vs. 6.3 ± 0.5 ml, respectively), as well as the enhanced suppression of intake by CCK plus gastric load (6.9 ± 0.6 vs. 4.6 ± 0.5 ml, respectively). These findings demonstrate that CCK-induced activation of 5-HT3 receptors requires gastric, but not intestinal feedback.

Intracerebroventricular administration of MK-801 increases food intake through mechanisms independent of gastric emptying

2004 ◽  
Vol 287 (6) ◽  
pp. R1462-R1467 ◽  
Author(s):  
M. Covasa ◽  
Chun-Yi Hung ◽  
R. C. Ritter ◽  
G. A. Burns
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Meal Size ◽  
Sucrose Intake ◽  
Intracerebroventricular Administration ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Parallel Experiment

Systemic or hindbrain administration of MK-801, a noncompetitive N-methyl-d-aspartate receptor antagonist, increases meal size. To examine whether MK-801 enhances intake by increasing gastric emptying, we administered MK-801 (2.0 μg/3.0 μl) into the fourth ventricle [intracerebroventricular (ICV)] and measured feeding and gastric emptying of 5-ml NaCl or 15% sucrose loads. In a parallel experiment, we examined food intake and gastric emptying following intraperitoneal (IP) injection of MK-801 (100 μg/kg). MK-801, either IP or ICV, increased 30-min sucrose intake compared with control (12.3 ± 0.7 vs. 9.8 ± 0.5 and 16.6 ± 2.0 vs. 10.7 ± 0.7 ml, for IP and ICV administration, respectively). Also, IP MK-801 increased 5-min gastric emptying of NaCl (4.13 ± 0.1 ml emptied) and sucrose (3.11 ± 0.1 ml emptied) compared with control (3.75 ± 0.2 and 2.28 ± 0.1 ml emptied for NaCl and sucrose loads, respectively). In contrast, ICV MK-801 did not alter NaCl emptying (3.82 ± 0.1 ml emptied) compared with control (3.82 ± 0.3 ml emptied) and actually reduced gastric emptying of sucrose (2.1 ± 0.2 and 2.94 ± 0.1 ml emptied, for MK and vehicle, respectively). These data confirm previous results that systemic as well as hindbrain injection of MK-801 increases food intake. However, because ICV MK-801 failed to increase gastric emptying, these results indicate that MK-801 increases food intake through mechanisms independent of altered gastric emptying.

scholarly journals Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

2019 ◽  
Vol 20 (10) ◽  
pp. 2452 ◽  
Author(s):  
Martha López-Canul ◽  
Seung Hyun Min ◽  
Luca Posa ◽  
Danilo De Gregorio ◽  
Annalida Bedini ◽  
...  
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Partial Agonist ◽  
Receptor Subtypes ◽  
Dark Phase ◽  
Light Phase ◽  
Dark Cycle ◽  
Simultaneous Activation ◽  
Type 3 ◽  
G Protein Coupled

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.

scholarly journals Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

2011 ◽  
Vol 301 (2) ◽  
pp. R448-R455 ◽  
Author(s):  
Jason Wright ◽  
Carlos Campos ◽  
Thiebaut Herzog ◽  
Mihai Covasa ◽  
Krzysztof Czaja ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Nmda Receptor Antagonist ◽  
Behavioral Pattern ◽  
Vagal Afferents ◽  
Nmda Receptor Antagonists ◽  
The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

scholarly journals Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight

2005 ◽  
Vol 29 (12) ◽  
pp. 1402-1412 ◽  
Author(s):  
K Malmlöf ◽  
F Zaragoza ◽  
V Golozoubova ◽  
H H F Refsgaard ◽  
T Cremers ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Neural Activity ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

GSK1614343, a Novel Ghrelin Receptor Antagonist, Produces an Unexpected Increase of Food Intake and Body Weight in Rodents and Dogs

2011 ◽  
Vol 94 (2) ◽  
pp. 158-168 ◽  
Author(s):  
Vivian J.A. Costantini ◽  
Elena Vicentini ◽  
Fabio M. Sabbatini ◽  
Enzo Valerio ◽  
Stefano Lepore ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Ghrelin Receptor ◽  
Ghrelin Receptor Antagonist
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