Centrally administered neuropeptide Y delays gastric emptying via Y<sub>2</sub>receptors in rats

Ishiguchi, Tadashi; Amano, Taku; Matsubayashi, Hiroaki; Tada, Hitoshi; Fujita, Mikio; Takahashi, Toshio

doi:10.1152/ajpregu.2001.281.5.r1522

Cited by 55 publications

(65 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Findings include 1) peripherally administered PYY (1-36) binds in a saturable manner to specific areas in the DVC (23) and induces c-Fos immunoreactivity in these areas (6); 2) PYY(1-36) and NPY(3-36) (a Y 2 agonist) dose dependently inhibit excitatory postsynaptic currents in cholinergic neurons of the dorsal motor nucleus of the vagus (10); 3) injection of PYY or Y 2 agonists [NPY or PYY ] into the DVC inhibits neurons of the dorsal motor nucleus of the vagus, as well as TRH-induced gastric motility (11,12,14); 4) intracisternal injections of PYY(1-36) inhibit gastric emptying, and this inhibition is attenuated by vagotomy (13); and 5) intracerebroventricular injection of NPY(3-36) (Y 2 agonist) dose dependently delays gastric emptying of solids, as well as impairs antral contractions and antropyloric coordination in the emptying period (25). In contrast to these Y 2 receptor-dependent effects, Y 1 receptor-mediated effects on gastric emptying appear to be stimulatory.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Chelikani

Haver²,

Reidelberger³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

We compared the effects of the two molecular forms of the brain-gut peptide YY (PYY), PYY(1-36) and PYY(3-36), on gastric emptying. Unanesthetized rats received 20-min intravenous infusions of rat PYY(1-36) (0, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and rat PYY(3-36) (0, 0.5, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), either alone or combined, and gastric emptying of saline was measured during the last 10 min of infusion. For comparison, human PYY(3-36) was administered at 0, 17, and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . Gastric emptying was decreased by 11, 24, 26 and 38% in response to 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(1-36); by 10, 26, 41, 53, and 57% in response to 5, 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(3-36); and by 35 and 53% in response to 17 and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of human PYY(3-36), respectively. Estimated ED50s were 470 and 37 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 for rat PYY(1-36) and PYY(3-36), respectively. In general, within an experiment, coadministration of PYY(1-36) and PYY(3-36) inhibited gastric emptying by an amount that was comparable to that produced when either peptide was given alone. We conclude that 1) intravenous infusion of PYY(1-36) and PYY(3-36) each produces a dose-dependent inhibition of gastric emptying in rats, 2) PYY(3-36) is an order of magnitude more potent than PYY(1-36) in inhibiting gastric emptying, 3) human PYY(3-36) and rat PYY(3-36) inhibit gastric emptying similarly, and 4) PYY(1-36) and PYY(3-36) do not appear to interact in an additive or synergistic manner to inhibit gastric emptying. intravenous infusion; dose response; interaction PEPTIDE YY (PYY), neuropeptide Y (NPY), and pancreatic polypeptide (PP) comprise the "PP-fold" family of structurally related brain-gut peptides. PYY is synthesized in the gastrointestinal tract, as well as in the central and peripheral nervous systems. Endocrine cells of the ileum, colon, and rectum provide a major source of PYY (2, 47). PYY has also been detected in gastric mucosa, pancreatic islets, myenteric and serosal ganglia, sympathetic neurons, adrenal gland, spinal cord, and brain, including the hypothalamus, pituitary, pons, medulla oblongata, and the brain stem (7-9, 15, 16, 22, 30, 32, 37).Food intake releases PYY into the circulation (2, 47). Systemic administration of PYY inhibits food intake, gastric emptying, intestinal fluid and electrolyte secretion, gallbladder contraction, and exocrine pancreatic secretion (5, 36). Whether PYY acts physiologically by endocrine, neurocrine, and/or paracrine mechanisms to produce these effects remains to be determined. If PYY acts as a blood-borne hormonal signal to produce an effect, then it is important to determine whether the effect is produced by intravenous doses of PYY that reproduce meal-induced increases in plasma PYY.The two major molecular forms of PYY found in the gut and circulation are PYY(1-36) and PYY(3-36) (19 -21). In humans, plasma concentrations of PYY were reported to be 11 pM in the fasted state with PYY(3-36) contributing 37% ...

show abstract

Section: Discussionmentioning

confidence: 99%

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Chelikani

Haver²,

Reidelberger³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Both types of rats were randomly divided into two equal groups to be administered with vehicle (0.25% Tween 80 and 0.5% methylcellulose dissolved in water) or DVS at a dose of 30 mg/kg. Gastric emptying in each rat was measured using a previously established method briefly described below (13).…”

Section: Experimental Protocolsmentioning

confidence: 99%

Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

Dai

Lei

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Desvenlafaxine succinate (DVS) is a novel serotonin and norepinephrine reuptake inhibitor. The aim of this study was to investigate the effects of DVS on visceral hypersensitivity and solid gastric emptying in a rodent model of gastric hyperalgesia. Twenty-eight gastric hyperalgesia rats and 20 control rats were used. Visceral sensitivity during gastric distention (GD) was assessed by recording of electromyogram (EMG) at pressures of 20, 40, 60, and 80 mmHg. DVS with doses of 1, 10, and 30 mg/kg were administrated by gavage, 5-HT1A antagonist (WAY-100635, 0.3 mg/kg) was given subcutaneously, and 5-HT2A antagonist (ketanserin, 1 mg/kg) was given intraperitoneally. The level of norepinephrine in plasma was measured by enzymelinked immunosorbent assay. We found that 1) visceral hypersensitivity induced by acetic acid was validated. 2) DVS dose-dependently reduced visceral hypersensitivity in the gastric hypersensitivity rats. The EMG (% of baseline value without GD) during GD at 60 and 80 mmHg with DVS at a dose of 30 mg/kg were 119.4 Ϯ 2.3% (vs. saline 150.9 Ϯ 2.7%, P Ͻ 0.001) and 128.2 Ϯ 3.2% (vs. saline 171.1 Ϯ 2.4%, P Ͻ 0.001). Similar findings were observed at a dose of 10 mg/kg. DVS at a dose of 1 mg/kg reduced visceral hypersensitivity only during GD at 60 mmHg. 3) Neither WAY-100635 nor ketanserin blocked the effect of DVS on visceral sensitivity. 4) DVS at 30 mg/kg significantly increased plasma NE level (P ϭ 0.012 vs. saline). 5) DVS at 30 mg/kg significantly delayed solid gastric emptying (P Ͻ 0.05 vs. saline). We conclude that DVS reduces visceral sensitivity in a rodent model of visceral hypersensitivity and delays solid gastric emptying. Caution should be made when DVS is used for treating patients.antidepressant; visceral hypersensitivity; gastric emptying; desvenlafaxine succinate FUNCTIONAL DYSPEPSIA (FD) is a common clinical gastrointestinal disease with a high prevalence throughout the world (23, 27), defined as pain or discomfort located in the upper abdomen without evidence of organic structural abnormalities that can explain the symptoms (36). FD is considered to be a biopsychosocial disorder with visceral hypersensitivity, impaired gastroduodenal motility, and central nervous system disturbance (34, 35). Psychosocial factors can affect visceral sensation and gut motility (34,35). Antidepressants are widely prescribed in patients with FD in clinic (12,33,38). These drugs may modulate several aspects in FD such as improving psychiatric and psychological conditions, influencing central regulation of visceral pain stimuli, and modifying gut sensorimotor function (2-4). In previous studies, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were used to treat FD (21, 37, 43).Desvenlafaxine succinate (DVS) is the third serotonin-norepinephrine reuptake inhibitor approved by the Food and Drug Administration for the treatment of major depressive disorders in 2008 (19). It increases the level of serotonin (5-HT) and norepinephrine (NE) by blocking the presynaptic reup...

show abstract

“…Although systemic administration of ghrelin accelerates gastric emptying (6,14), the simultaneous occurrence of enhanced distal stomach motility and proximal stomach relaxation must be critical to the functional outcome of accelerated gastric emptying. Because actual transit of food into the duodenum is necessary for relaxation of the pyloric sphincter, which coordinates with antral contraction during the emptying period (40 -60 min after feeding) (13), temporal and precise analyses are required to know the effect of ghrelin on the actual transit of food into the duodenum.…”

Section: Ghrelin Induced Relaxation Of the Proximal Stomach And Stimumentioning

confidence: 99%

Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat

Kobashi

Yanagihara

Fujita³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

appetite; vagus; fundus; stomach; medulla GHRELIN IS A RECENTLY IDENTIFIED endogenous ligand for growth hormone secretagogue receptor (GHS-R) and was originally isolated from the stomach (19). In addition to GH-releasing activity, ghrelin has an orexigenic (appetite-enhancing) effect. This is very reasonable, since the blood ghrelin level rose sharply just before onset of the dark phase, and the stomach ghrelin level was high during fasting in rats (30). Ghrelin has been shown to be present not only in the stomach but also in the hypothalamus, and it participates in the regulation of food intake itself and feeding-related phenomena through the peripheral and central nervous system (5, 25). Since feeding is closely related to digestive function, the effects of orexigenic peptides on gastric acid secretion, bile secretion, and gastric motility have been well investigated (3,10,15,18,20,24,29,35). Orexigenic peptides generally stimulate gastric acid secretion (23,24,33) and phasic contractions of the distal stomach (3,15,20,23), which enhance the ability to churn the gastric contents to accelerate gastric emptying; these gastric functions are particularly important for digestion. Accommodation of food is also important for smooth digestion, and impaired accommodation is thought to be one of the factors inducing meal-related symptoms, such as functional dyspepsia (31). The proximal region of the stomach, which serves as a reservoir, relaxes to accommodate food and fluid during swallowing (2, 17). Our previous studies revealed that fourth ventricular administration (and/or intramedullary injections) of orexin-A and neuropeptide Y (NPY), which are well-known orexigenic peptides, induced relaxation of the proximal stomach to facilitate the reservoir function of the stomach (15, 18).Ghrelin, as well as other orexigenic peptides, controls gastric functions. Intravenous administration of ghrelin stimulates gastric acid secretion and gastric motility in rats (23). Central and peripheral administration of ghrelin induced fasted motor activity of the gastrointestinal tract in rats (8). Histological study confirmed GHS-R mRNA expression in several hypothalamic nuclei, many of which have long been recognized as playing roles in body weight and food intake in rats and mice (37). In addition, GHS-R mRNA has also been found in the dorsal vagal complex (DVC), including the area postrema (AP), nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMV). Immunohistochemical study revealed that GHS-R was expressed in the NST and DMV in rats (22). Microinjection of ghrelin into the DVC facilitated food intake (7). Since the DVC is the center for controlling gastric motility, it is plausible that ghrelin induces relaxation of the proximal stomach, as well as other orexigenic peptides, as shown in our previous studies (15,18). Additionally, recent studies revealed that the intermediate and caudal DMV contain different groups of preganglionic neurons (21, 36). It is well known that the caudal part of the DMV is involv...

show abstract

Centrally administered neuropeptide Y delays gastric emptying via Y₂receptors in rats

Cited by 55 publications

References 27 publications

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat

Contact Info

Product

Resources

About

Centrally administered neuropeptide Y delays gastric emptying via Y2receptors in rats

Cited by 55 publications

References 27 publications

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat

Contact Info

Product

Resources

About

Centrally administered neuropeptide Y delays gastric emptying via Y₂receptors in rats