Bombesin affects feeding independent of a gastric mechanism or site of action

1989 ◽  
Vol 257 (5) ◽  
pp. R1219-R1224
Author(s):  
A. M. Hostetler ◽  
P. R. McHugh ◽  
T. H. Moran
Keyword(s):  
Gastric Emptying ◽  
Rank Order ◽  
Dose Range ◽  
Relative Potency ◽  
Inhibitory Mechanism ◽  
Relative Affinity ◽  
Site Of Action ◽  
Inhibit Food Intake ◽  
Feeding Effects ◽  
Bombesin Receptors

Peripherally administered bombesin has been demonstrated to inhibit food intake in a variety of species. Although the behavioral actions of bombesin are well characterized, neither the site of action nor mechanism through which bombesin affects feeding has been demonstrated. To test the hypothesis that bombesin's feeding effects are through a gastric inhibitory mechanism or a gastric site of action we examined the potential relationship between the inhibition of gastric emptying and the inhibition of intake produced across a dose range of bombesin and compared the relative potency of bombesin analogues for inhibiting feeding with their affinity for gastric bombesin receptors. Comparisons of the inhibitions of gastric emptying and feeding produced by 2, 4, 8, or 16 micrograms/kg of bombesin revealed no relationship, and, in fact, no gastric inhibitory action was evident. The feeding inhibitory actions of dose ranges (100 pmol-100 nmol) of litorin, ranatensin, acetylated gastrin-releasing peptide-(20-27) [AcGRP-(20-27)] and bombesin-(8-14) fragment were assessed and compared with bombesin. These compounds inhibited feeding with a relative potency of bombesin greater than AcGRP-(20-27) greater than ranatensin greater than litorin greater than bombesin-(8-14). This rank order of potency differed from the relative affinity of these compounds for gastric bombesin receptors for which all of these compounds except bombesin-(8-14) have a greater affinity than does bombesin. The results of these two experiments suggest that bombesin's satiety actions are not mediated by a gastric inhibitory mechanism or through a gastric site of action.

Peptide YY(3–36) inhibits gastric emptying and produces acute reductions in food intake in rhesus monkeys

2005 ◽  
Vol 288 (2) ◽  
pp. R384-R388 ◽  
Author(s):  
Timothy H. Moran ◽  
Ulrika Smedh ◽  
Kimberly P. Kinzig ◽  
Karen A. Scott ◽  
Susan Knipp ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Rhesus Monkeys ◽  
Food Access ◽  
Peptide Yy ◽  
Human Subjects ◽  
Dose Range ◽  
Suppressive Effect ◽  
Reduce Food Intake ◽  
Inhibit Food Intake

Peptide YY3–36 [PYY(3–36)], a gastrointestinal peptide that is released into the circulation in response to ingesting a meal, has recently been suggested to play a role in controlling food intake. PYY(3–36) has been reported to inhibit food intake following peripheral administration in rodents and in human subjects. To more fully characterize the potential feeding actions of PYY(3–36), we examined the ability of a dose range of PYY(3–36) (0.3–3.0 nmol/kg) to affect liquid gastric emptying and daily 6-h food intake in male rhesus monkeys. Intramuscular PYY(3–36) produced a dose-related inhibition of saline gastric emptying that was maximal at a dose of 3 nmol/kg. Intramuscular PYY(3–36) administered before daily 6-h food access produced significant feeding reductions at doses of 1 and 3 nmol/kg. Analyses of the patterns of food intake across the 6-h period of food access revealed that PYY(3–36) increased the latency to the first meal and reduced average meal size without altering meal number. Although single doses of PYY(3–36) reduced intake, a suppressive effect on food intake was not sustained over multiple administrations across successive days. Together, these data suggest that PYY(3–36) has the ability to reduce food intake in acute test situations in nonhuman primates. Whether this is a physiological action of the endogenous peptide remains to be determined.

Gastric loads potentiate inhibition of food intake produced by a cholecystokinin analogue

1991 ◽  
Vol 261 (5) ◽  
pp. R1141-R1146 ◽  
Author(s):  
G. J. Schwartz ◽  
L. A. Netterville ◽  
P. R. McHugh ◽  
T. H. Moran
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Threshold Dose ◽  
Gastric Distension ◽  
Cck Receptors ◽  
Load Combination ◽  
Glucose Intake ◽  
Dose Dependent Fashion ◽  
Inhibit Food Intake ◽  
Long Acting

We have proposed that cholecystokinin's (CCK) inhibition of gastric emptying contributes to its ability to inhibit food intake. To directly test this hypothesis in rats, the effect of the presence of a 5-ml gastric saline load on the ability of a long-acting cholecystokinin analogue U-67827E (0.1-10.0 nmol/kg) to inhibit intake of a 0.5 kcal/ml glucose solution was measured. The CCK analogue alone inhibited intake at a threshold dose of 2.5 nmol/kg. Although lower doses of the CCK analogue alone had no effect on subsequent glucose intake, when combined with the gastric load such doses did significantly inhibit intake. Thus the presence of a gastric load reduced the threshold dose of the CCK analogue required to inhibit intake. Furthermore, at suprathreshold doses, the peptide-load combination suppressed intake more than the peptide alone. In addition, administration of 0.5 and 5.0 nmol/kg doses of the CCK analogue inhibited gastric emptying at 10, 20, and 30 min in a dose-dependent fashion. The CCK analogue's inhibition of food intake and gastric emptying were reversed by pretreatment with 100 micrograms/kg L364,718, indicating that the analogue was having its effects by interacting with specific type A CCK receptors. Together these data support the notion that CCK satiety derives from an integration of the visceral afferent signals generated by CCK's promotion of gastric distension and those produced directly by CCK.

A central site of action for benzamide facilitation of gastric emptying

1983 ◽  
Vol 91 (2-3) ◽  
pp. 197-205 ◽  
Author(s):  
Brenda Costall ◽  
Simon J. Gunning ◽  
Robert J. Naylor ◽  
Karen H. Simpson
Keyword(s):  
Gastric Emptying ◽  
Site Of Action

THE INHIBITORY ACTION OF NATURAL AND SYNTHETIC GLUCOCORTICOIDS ON ADRENAL STEROIDOGENESIS AT THE ADRENAL LEVEL

1963 ◽  
Vol 27 (1) ◽  
pp. 123-126 ◽  
Author(s):  
GY. FEKETE ◽  
P. GÖRÖG
Keyword(s):  
Inhibitory Action ◽  
Regulatory Mechanism ◽  
Relative Potency ◽  
Inflammatory Activity ◽  
Inhibitory Mechanism ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis ◽  
Synthetic Glucocorticoids ◽  
Natural And Synthetic

SUMMARY Experiments are described which show that the in vitro synthesis of corticosterone under the influence of ACTH is inhibited by hydrocortisone, prednisolone and dexamethasone and that the relative potency of these three substances corresponds to their relative clinical anti-inflammatory activity. It is suggested that a direct adrenal inhibitory mechanism plays a physiological and pharmacological role, in addition to the regulatory mechanism controlling adrenal steroid function mediated by the pituitary.

The dorsal vagal complex as a site for cocaine- and amphetamine-regulated transcript peptide to suppress gastric emptying

2006 ◽  
Vol 291 (1) ◽  
pp. R124-R130 ◽  
Author(s):  
Ulrika Smedh ◽  
Timothy H. Moran
Keyword(s):  
Gastric Emptying ◽  
Fourth Ventricle ◽  
Corticotropin Releasing Factor ◽  
Dorsal Vagal Complex ◽  
Central Administration ◽  
Inhibitory Effects ◽  
Gastric Motor Function ◽  
Site Of Action ◽  
A Site ◽  
Dorsal Hindbrain

Cocaine- and amphetamine-regulated transcript-derived peptides (CARTp) and corticotropin-releasing factor (CRF) alter feeding and gastrointestinal function after central administration, and the gastric inhibitory effects are mediated through CRF. We hypothesized that dorsal hindbrain effects of CARTp on gastric emptying are mediated by the vagus nerve and that the dorsal vagal complex (DVC) is a site of action for the gastric inhibitory effects of both CARTp and CRF. Rats were equipped with chronic intragastric fistulas and guide cannulas aimed at the fourth ventricle or the DVC. Fourth intracerebroventricular CARTp-induced suppression of 12 ml glucose (12.5%) gastric emptying during fill was blocked by subdiaphragmatic vagotomy. To establish whether the DVC may be a site of action for CARTp and/or CRF, intraparenchymal microinjections (0.25 μl) of CARTp (0.1 and 0.5 μg) and CRF (5 and 10 pmol) were administered in the DVC. Each dose, previously shown to be ineffective after fourth intracerebroventricular administration, suppressed gastric emptying during gastric fill vs. vehicle, but neither peptide changed gastric secretion volume or gastric acidity. The results indicate that the DVC is a target site for CRF and CARTp to inhibit gastric emptying and that the vagus mediates dorsal hindbrain effects of CARTp on gastric motor function.

Gastric and nongastric mechanisms for satiety action of cholecystokinin

1988 ◽  
Vol 254 (4) ◽  
pp. R628-R632 ◽  
Author(s):  
T. H. Moran ◽  
P. R. McHugh
Keyword(s):  
Gastric Emptying ◽  
Linear Relationship ◽  
Inhibitory Action ◽  
Glucose Solution ◽  
Dose Range ◽  
Quantitative Relationship ◽  
Dilution Method ◽  
Sprague Dawley ◽  
Testing Period ◽  
Sprague Dawley Rats

The quantitative relationship between cholecystokinin's (CCK) inhibitory actions on gastric emptying and feeding was examined in rats. CCK (1, 2, 4, or 8 micrograms/kg) inhibited both the gastric emptying (determined by the dye dilution method) and ingestion of a 0.5-kcal/ml glucose solution in a 30-min testing period in 20-h deprived male Sprague-Dawley rats. Comparisons of the inhibitions of gastric emptying and feeding across the dose range of CCK revealed two components of CCK satiety: one defined by a linear relationship between the gastric inhibitory and feeding inhibitory actions of CCK through a dose range of 1-4 micrograms/kg, which accounted for 64% of the variability in the satiety action of CCK, and a second that appeared to be independent of the gastric inhibitory action of CCK.

Inhibition of gastric emptying by acids depends on pH, titratable acidity, and length of intestine exposed to acid

1990 ◽  
Vol 259 (6) ◽  
pp. G1025-G1030 ◽  
Author(s):  
H. C. Lin ◽  
J. E. Doty ◽  
T. J. Reedy ◽  
J. H. Meyer
Keyword(s):  
Small Intestine ◽  
Lactic Acid ◽  
Gastric Emptying ◽  
Feedback Control ◽  
Titratable Acidity ◽  
Inhibitory Mechanism ◽  
Inhibitory Effects ◽  
Maximal Inhibition ◽  
Relative Contribution ◽  
Decreasing Ph

Exposure of the small intestine to acid inhibits gastric emptying in a dose-related fashion that depends on titratable acidity and pH. Little information is available on the location of this inhibitory mechanism or on the relative contribution of titratable acidity and pH to this feedback control. We hypothesized that the dependence on titratable acidity is related to the length of the intestine exposed to acid and that the dependence on pH is related to the region of the intestine exposed to acid. To test these ideas, we studied 11 dogs with duodenal and jejunal fistulas. The inhibitory effects were tested when different lengths of the small intestine were exposed to test solutions of 0.03, 0.06, and 0.12 meq/ml titratable acidities. pH as an independent covariable was separated from titratable acidity by comparing the inhibition of gastric emptying of lactic acid (pH fixed to 2.4) to HCl (pH 0.96-1.6). Maximal inhibition of gastric emptying by both acids depended on acid exposure of a length of small intestine that was greater than 65 but less than or equal to 150 cm long. When acid was confined to the proximal 15 cm, increasing concentration of HCl (decreasing pH) resulted in increasing inhibition, but this effect was absent with increasing concentration of lactic acid (fixed pH). Inhibition was absent when 0.06 meq/ml HCl was infused into the intestine beyond the midintestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneity of Human Vascular Pre- and Post-Synaptic α-Adrenoceptors

1981 ◽  
Vol 61 (s7) ◽  
pp. 203s-206s ◽  
Author(s):  
M. J. Stevens ◽  
R. E. Rittinghausen ◽  
R. F. W. Moulds
Keyword(s):  
Transmitter Release ◽  
Rank Order ◽  
Relative Potency ◽  
Maximum Response ◽  
Homogeneous Population ◽  
Receptor Agonists ◽  
Postsynaptic Receptors ◽  
Arteries And Veins ◽  
Receptor Agonists And Antagonists

1. The effects of various α-receptor agonists and antagonists on pre- and post-synaptic α-receptors of human isolated digital arteries and metacarpal (or metatarsal) veins have been studied. 2. The relative potency of phenylephrine compared with noradrenaline on the postsynaptic receptors was significantly greater in arteries than in veins. 3. The rank order of potency of various α-agonists on postsynaptic receptors was the same in arteries and veins except that in veins adrenaline was more potent than clonidine, whereas the reverse was the case in arteries. 4. Phentolamine showed no selectivity in either antagonizing postsynaptic responses or enhancing stimulation-induced transmitter release by antagonism at presynaptic α-receptors. 5. Yohimbine potently, but not selectively, antagonized postsynaptic responses to noradrenaline and phenylephrine in both arteries and veins, and enhanced stimulation-induced transmitter release to a greater extent in arteries than in veins. 6. Prazosin reduced the maximum response to noradrenaline (but not phenylephrine) to a significantly greater extent in veins than in arteries, and in veins alone shifted the phenylephrine curve to a greater degree than it did the noradrenaline curve. Prazosin did not significantly increase stimulation-induced transmitter release in either arteries or veins. 7. Phenoxybenzamine produced large increases in stimulation-induced tritium outflow which were significantly greater in arteries than in veins (even in the presence of cocaine). 8. It is concluded firstly that the postsynaptic α-adrenoceptors of these tissues are not a homogeneous population and that differing proportions of these receptors are present in the digital arteries and the metacarpal veins, and secondly that the sensitivities of the presynaptic α-adrenoceptors in the two tissues may also be different.

scholarly journals Adaptation to high-fat diet reduces inhibition of gastric emptying by CCK and intestinal oleate

2000 ◽  
Vol 278 (1) ◽  
pp. R166-R170 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter
Keyword(s):  
Gastric Emptying ◽  
High Fat Diet ◽  
Intraperitoneal Injection ◽  
Dose Range ◽  
Significant Inhibition ◽  
Similar Degree ◽  
High Fat ◽  
Intraduodenal Infusion ◽  
Vehicle Injection ◽  
Nacl Load

Rats maintained on low-fat (LF) or high-fat (HF) diets were fitted with gastric cannulas and duodenal catheters. Intraperitoneal injection of 0.250–2.0 μg/kg cholecystokinin (CCK) significantly inhibited gastric emptying of a 5-ml NaCl load in LF rats by 26.2–55.1% compared with emptying after vehicle injection. By contrast, CCK-induced inhibition of gastric emptying was significantly less in HF rats given the same CCK doses (10.0–31.7% inhibition over the same CCK dose range). A 20-min intraduodenal infusion of oleate (0.03 or 0.06 kcal/ml) also resulted in significant inhibition of gastric emptying in LF rats (24 and 89%, respectively). Oleate-induced inhibition of gastric emptying was significantly attenuated in rats maintained on the HF diet (2 and 56%, respectively). Unlike CCK injections or oleate infusion, intraduodenal maltotriose infusion inhibited gastric emptying to a similar degree in LF and HF rats (77 and 78%, respectively). These results indicate that feeding HF diets diminishes the enterogastric inhibition of gastric emptying by intestinal oleate and diminishes the ability of CCK to inhibit gastric emptying.

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