Blockade of type A, not type B, CCK receptors attenuates satiety actions of exogenous and endogenous CCK

1992 ◽  
Vol 262 (1) ◽  
pp. R46-R50 ◽  
Author(s):  
T. H. Moran ◽  
P. J. Ameglio ◽  
G. J. Schwartz ◽  
P. R. McHugh
Keyword(s):  
Food Intake ◽  
Glucose Consumption ◽  
Type A ◽  
Type B ◽  
Inhibitory Effects ◽  
Cck Receptors ◽  
Glucose Intake ◽  
Baseline Levels ◽  
Endogenous Release ◽  
Cck Receptor Antagonists

Recent work has suggested a role for an endogenous release of cholecystokinin (CCK) acting at either type A or type B CCK receptors in the control of food intake. In an effort to investigate whether the mechanisms by which exogenously administered and endogenously released CCK inhibits food intake are similar and depend upon interactions with either type A or type B CCK receptors, we examined in rats the ability of the type A (L 364718) and type B (L 365260) CCK receptor antagonists to 1) block the inhibition of glucose consumption produced by an intraperitoneal injection of 4 micrograms/kg of CCK and 2) increase glucose consumption in the absence of exogenous CCK after a 6-h daytime deprivation. Increasing dosages (10-100 micrograms/kg) of the type A CCK antagonist resulted in a dose-related blockade of the inhibition of intake produced by CCK, and the 100 micrograms/kg dose of the A antagonist significantly increased glucose intake above baseline levels. In contrast, no dose (10-1,000 micrograms/kg) of the B antagonist blocked the inhibitory action of exogenous CCK at any time point. In the absence of exogenous CCK, the 32 and 100 micrograms/kg doses of L 364718 increased intake above baseline levels. No dose (3.2-320 micrograms/kg) of the type B antagonist, L 365260, affected intake in this paradigm. These results suggest that the mediation of the feeding-inhibitory effects of exogenous and endogenous CCK are similar and depend upon activation of type A CCK receptors.

Blockade of type A, but not type B, CCK receptors postpones satiety in rhesus monkeys

1993 ◽  
Vol 265 (3) ◽  
pp. R620-R624 ◽  
Author(s):  
T. H. Moran ◽  
P. J. Ameglio ◽  
H. J. Peyton ◽  
G. J. Schwartz ◽  
P. R. McHugh
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Rhesus Monkeys ◽  
Type A ◽  
Intragastric Administration ◽  
Maximal Effect ◽  
Type B ◽  
Cck Receptors ◽  
Total Food Intake ◽  
Cck Receptor Antagonist

The exogenous administration of the brain/gut peptide cholecystokinin (CCK) inhibits food intake in a variety of species, including subhuman primates and humans. To determine the role of endogenously released CCK in the control of food intake in rhesus monkeys, we examined the ability of the selective type A and type B CCK antagonists devazepide and L-365260 to affect total daily food intake and various meal patterns. Various doses of the antagonists were administered intragastrically 30 min before a daily 4-h feeding period. One-gram food pellets were delivered in response to lever pulls, and intake was computer monitored. Intragastric administration of the type A CCK receptor antagonist devazepide (10-320 micrograms/kg) significantly increased food intake in a dose-related fashion. The threshold for increasing intake was 32 micrograms/kg, and a maximal effect was obtained at a dose of 100 micrograms/kg that increased total 4-h food intake by 47%. The effect of devazepide on food intake was mediated by significant increases in the size and duration of the initial meal, lengthening of the subsequent intermeal interval, and a decrease in the satiety ratio (intermeal interval/1st meal size). In contrast, intragastric administration of the type B CCK receptor antagonist L-365260 (3.2-320 micrograms/kg) did not significantly affect total food intake or any of the meal parameters. These data demonstrate that endogenously released CCK acting through type A CCK receptors plays a role in regulating food intake in rhesus monkeys.

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.

Dual effects of acupuncture on gastric motility in conscious rats

2003 ◽  
Vol 285 (4) ◽  
pp. R862-R872 ◽  
Author(s):  
Makoto Tatewaki ◽  
Mary Harris ◽  
Kenichiro Uemura ◽  
Tomio Ueno ◽  
Etsuo Hoshino ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Type A ◽  
Peak Amplitude ◽  
Phase Iii ◽  
Type B ◽  
Inhibitory Effects ◽  
Complex Type ◽  
Motility Index ◽  
Conscious Rats ◽  
Strain Gauge Transducer

The effects of manual acupuncture on gastric motility were investigated in 35 conscious rats implanted with a strain gauge transducer. Twenty (57.1%) rats showed no cyclic groupings of strong contractions ( type A), whereas 15 (42.9%) rats showed the phase III-like contractions of the migrating motor complex ( type B) in the fasting gastric motility. Acupuncture at the stomach (ST)-36 (Zusanli), but not on the back [Weishu, bladder (BL)-21], increased the peak amplitude of contractions to 172.4 ± 25.6% of basal in the type A rats ( n = 20, P < 0.05). On the other hand, the motility index for 60 min after the acupuncture was not affected by the acupuncture in this group. On the contrary, acupuncture decreased the peak amplitude and motility index to 72.9 ± 14.0% and 73.6 ± 16.2% in the type B rats ( n = 15, P < 0.05), respectively. The stimulatory and inhibitory effects of acupuncture observed in each type were reproducible on the separate days. In 70% of type A rats, acupuncture induced strong phase III-like contractions lasting for over 3 h that were abolished by atropine, hexamethonium, atropine methyl bromide, and vagotomy. Naloxone significantly shortened the duration of the stimulatory effects from 3.52 ± 0.21 to 1.02 ± 0.15 h ( n = 3, P < 0.05). These results suggest that acupuncture at ST-36 induces dual effects, either stimulatory or inhibitory, on gastric motility. The stimulatory effects are mediated in part via vagal efferent and opioid pathways.

CCK is involved in both peripheral and central mechanisms controlling food intake in chickens

1997 ◽  
Vol 272 (1) ◽  
pp. R334-R340 ◽  
Author(s):  
A. Rodriguez-Sinovas ◽  
E. Fernandez ◽  
X. Manteca ◽  
A. G. Fernandez ◽  
E. Gonalons
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Receptor Type ◽  
Receptor Antagonists ◽  
Cck Receptors ◽  
High Affinity ◽  
Increase Food Intake ◽  
Cck Receptor Antagonist ◽  
Cck Receptor Antagonists ◽  
Voluntary Food Intake

The aim of this work was to study the involvement of cholecystokinin (CCK) in the control of food intake in chickens. The following aspects were studied: 1) the effects of intravenous and intracerebroventricular sulfated octapeptide of CCK (CCK-8s) on voluntary food intake; 2) the effects of two CCK-receptor antagonists. L-365,260 and L-364,718, on food intake; and 3) the ability of such drugs to block the effects of CCK-8s on food intake in the chicken. Intravenous and intracerebroventricular CCK-8s caused a decrease in food intake. Intraperitoneal L-365,260, a CCK-receptor antagonist with low affinity for the two CCK receptors described in the chicken, increases food intake. Intracerebroventricular L-364,718, a drug that has high affinity for the chicken central CCK-receptor type, increased food intake. The effect of intravenous CCK-8s on food intake was not blocked by L-364,718 or L-365,260, whereas that of intracerebroventricular CCK-8s was blocked by intracerebroventricular L-364,718. It is concluded that central endogenous CCK plays a role in the control of food intake, which is dependent on central CCK-receptor type; nevertheless, peripheral CCK also decreases food intake acting on the peripheral CCK-receptor type. The fact that intracerebroventricular L-364,718 is able to increase food intake is related to its high affinity for the central CCK-receptor type of this species. Finally, three different speculations that might explain the fact that intraperitoneal L-365,260 increases food intake are discussed.

CCK-8 decreases food intake and gastric emptying after pylorectomy or pyloroplasty

1988 ◽  
Vol 255 (1) ◽  
pp. R113-R116
Author(s):  
G. P. Smith ◽  
J. Falasco ◽  
T. H. Moran ◽  
K. M. Joyner ◽  
J. Gibbs
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Binding Sites ◽  
Specific Binding ◽  
Circular Muscle ◽  
Pyloric Sphincter ◽  
Inhibitory Effects ◽  
Cck Receptors ◽  
Adult Rat ◽  
Pyloric Muscle

Specific binding sites for cholecystokinin (CCK) in the gastrointestinal tract of the adult rat are limited to the gastroduodenal region and are concentrated in the circular muscle of the pyloric sphincter. To determine the relationship of these pyloric muscle binding sites to the inhibition by CCK of food intake and of gastric emptying, these inhibitory effects of CCK were investigated in rats that had the pyloric sphincter surgically removed or that had the pyloric sphincter contractile mechanism damaged by a pyloroplasty procedure. CCK-8 decreased food intake and gastric emptying significantly in rats after pylorectomy or pyloroplasty. This demonstrates that an intact pyloric sphincter is not necessary for these inhibitory effects in rats. Because we found autoradiographic evidence for CCK receptors near the gastroduodenal anastomosis, however, the results suggest either that these receptors mediated the inhibition of food intake and emptying by CCK-8 or that these effects depend on CCK receptors in other locations.

Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin

1997 ◽  
Vol 272 (4) ◽  
pp. R1245-R1251 ◽  
Author(s):  
T. H. Moran ◽  
A. R. Baldessarini ◽  
C. F. Salorio ◽  
T. Lowery ◽  
G. J. Schwartz
Keyword(s):  
Food Intake ◽  
Dose Range ◽  
Low Doses ◽  
Cck Receptors ◽  
Sham Surgery ◽  
Subdiaphragmatic Vagotomy ◽  
Glucose Intake ◽  
Vagal Afferent ◽  
Caudal Medulla

To assess the role of subdiaphragmatic vagal afferent and efferent fibers in the mediation of the inhibition of food intake by cholecystokinin (CCK), we compared the ability of a dose range (1-16 microg/kg), of CCK to affect 30-min liquid glucose (0.125 g/ml) intake in rats with either total subdiaphragmatic vagotomy, selective subdiaphragmatic vagal deafferentation, selective subdiaphragmatic vagal deefferentation, or sham surgery. Selective vagal deafferentation and deefferentations were produced by combinations of unilateral subdiaphragmatic vagotomy and contralateral afferent or efferent rootlet transection as fibers enter the caudal medulla. CCK produced a dose-related suppression of glucose intake in sham animals, and this action was eliminated in rats with total subdiaphragmatic vagotomy. CCK suppression of intake was attenuated in rats with vagal deafferentation, such that there was a loss of sensitivity to CCK. Vagal deefferentation resulted in lower levels of baseline intake and a truncation of the feeding-inhibitory actions of CCK. These data demonstrate that CCK's suppression of intake depends on actions of both vagal afferent and efferent fibers. We interpret these data as suggesting that 1) the actions of low doses of CCK depend on activation of vagal afferent CCK receptors and 2) the greater efficacy of higher CCK doses is the result of the potentiation of these vagal afferent actions due to local physiological gastrointestinal effects of the peptide that rely on vagal efferent input.

Biological and Morphological Studies on Low-Leukemia-Strain Mice with Hodgkin's-Like Neoplasia Induced by Serial Cell-Free Transmission of Leukemic Organs of SJL/J Strain Mice

1968 ◽  
Vol 26 ◽  
pp. 210-211
Author(s):  
S. Fujinaga ◽  
K. Maruyama ◽  
C.W. Williams ◽  
K. Sekhri ◽  
L. Dmochowski
Keyword(s):  
Tissue Culture ◽  
Type A ◽  
Reticulum Cell ◽  
Type B ◽  
Viral Origin ◽  
Serial Transfer ◽  
Strain Mouse ◽  
Morphological Studies ◽  
Cell Neoplasm ◽  
Free Material

Yumoto and Dmochowski (Cancer Res.27, 2098 (1967)) reported the presence of mature and immature type C leukemia virus particles in leukemic organs and tissues such as lymph nodes, spleen, thymus, liver, and kidneys of SJL/J strain mice with Hodgki's-like disease or reticulum cell neoplasm (type B). In an attempt to ascertain the possibility that this neoplasia may be of viral origin, experiments with induction and transmission of this neoplasm were carried out using cell-free extracts of leukemic organs from an SJL/J strain mouse with spontaneous disease.It has been possible to induce the disease in low-leukemia BALB/c and C3HZB strain mice and serially transfer the neoplasia by cell-free extracts of leukemic organs of these mice. Histological examination revealed the neoplasia to be of either reticulum cell-type A or type B. Serial transfer is now in its fifth passage. In addition leukemic spleen from another SJL/J strain mouse with spontaneous reticulum cell neoplasm (type A) was set up in tissue culture and is now in its 141st serial passage in vitro. Preliminary results indicate that cell-free material of 39th tissue culture passage can reproduce neoplasia in BALB/c mice.

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