Pylorectomy reduces the satiety action of cholecystokinin

1988 ◽  
Vol 255 (6) ◽  
pp. R1059-R1063 ◽  
Author(s):  
T. H. Moran ◽  
L. Shnayder ◽  
A. M. Hostetler ◽  
P. R. McHugh

Rat gastric cholecystokinin (CCK) receptors are localized to the circular muscle layer of the pyloric sphincter, and a role for these receptors in the mediation of CCK satiety has been proposed. To directly assess the contribution of this receptor population in CCK satiety, the area of the pyloric sphincter containing these receptors was surgically removed, and the behavioral responses to CCK were compared pre- and postpylorectomy. The presence of CCK receptors in the gastroduodenal junction was assessed by either in vitro CCK receptor autoradiography or in vitro contractile response to CCK. The results depended on the time after pylorectomy during which testing occurred. Two to 3 wk after pylorectomy rats demonstrated a significant attenuation of CCK satiety such that while the response to 1 and 2 micrograms/kg was intact, any additional inhibition by 4 and 8 micrograms/kg was eliminated. At this time, no evidence of CCK receptors around the gastroduodenal junction was found. In contrast, 2-3 mo after pylorectomy, the normal dose-response inhibition to CCK was intact. Evidence for the presence of CCK binding sites at the gastroduodenal junction was found by both autoradiography and physiological assessment. These results indicate a role for pyloric CCK receptors in the mediation of CCK satiety.

1991 ◽  
Vol 261 (3) ◽  
pp. R531-R535 ◽  
Author(s):  
T. H. Moran ◽  
R. J. Crosby ◽  
P. R. McHugh

The present study was designed to investigate a role for the pyloric sphincter and its population of cholecystokinin (CCK) receptors localized to the circular muscle layer in the inhibition of gastric emptying produced by exogenously administered CCK in rats. We examined the ability of two doses of CCK to inhibit the gastric emptying of 10-ml saline (0.9% NaCl) and glucose (0.125 g/ml) test meals in rats equipped with chronic gastric fistulas before and after surgical removal of the region of the pylorus containing CCK receptors. Preoperatively, CCK (2 and 8 micrograms/kg) inhibited gastric emptying of both saline and glucose. Pylorectomy did not significantly alter the baseline saline and glucose emptying and did not alter the ability of CCK to inhibit the emptying of the saline test meals. In contrast, pylorectomy eliminated the ability of CCK to inhibit glucose emptying. These results demonstrate that the inhibition of gastric emptying by CCK may involve multiple mechanisms depending on the character of the gastrointestinal contents.


1988 ◽  
Vol 255 (1) ◽  
pp. R113-R116
Author(s):  
G. P. Smith ◽  
J. Falasco ◽  
T. H. Moran ◽  
K. M. Joyner ◽  
J. Gibbs

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.


1984 ◽  
Vol 246 (1) ◽  
pp. R127-R130 ◽  
Author(s):  
G. T. Smith ◽  
T. H. Moran ◽  
J. T. Coyle ◽  
M. J. Kuhar ◽  
T. L. O'Donahue ◽  
...  

In an effort to identify target sites within the gastrointestinal (GI) tract through which cholecystokinin (CCK) may exert its gastric inhibitory and satiety effects, the distribution of CCK receptors was mapped in the stomach and small bowel by in vitro radiography utilizing 125I-labeled Bolton-Hunter CCK-33. Specific receptor binding was localized to the circular smooth muscle layer of the pyloric sphincter. Negligible binding was observed in the oblique, circular, or longitudinal muscle layers of other GI levels. Moderate nonspecific binding was associated with mucosal tissue in all gastric sections. The restriction of CCK receptors to the circular smooth muscle of the pyloric sphincter suggests this location as the site through which CCK inhibits gastric emptying. Gastric distension secondary to this inhibition may be the mechanism for CCK-induced satiety.


2006 ◽  
Vol 290 (6) ◽  
pp. G1307-G1317 ◽  
Author(s):  
Ling Cheng ◽  
Weibiao Cao ◽  
Claudio Fiocchi ◽  
Jose Behar ◽  
Piero Biancani ◽  
...  

Platelet-activating factor (PAF) and interleukin-6 (IL-6) are produced in the esophagus in response to HCl and affect ACh release, causing changes in esophageal motor function similar to esophagitis (Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289: G418–G428, 2005). We therefore examined HCl-activated mechanisms for production of PAF and IL-6 in cat esophageal mucosa and circular muscle. A segment of normal mucosa was tied at both ends, forming a mucosal sac (Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289: G860–G869, 2005) that was filled with acidic Krebs buffer (pH 5.8) or normal Krebs buffer (pH 7.0) as control and kept in oxygenated Krebs buffer for 3 h. The supernatant of the acidic sac (MS-HCl) abolished contraction of normal muscle strips in response to electric field stimulation. The inhibition was reversed by the PAF antagonist CV3988 and by IL-6 antibodies. PAF and IL-6 levels in MS-HCl and mucosa were significantly elevated over control. IL-6 levels in mucosa and supernatant were reduced by CV3988, suggesting that formation of IL-6 depends on PAF. PAF-receptor mRNA levels were not detected by RT-PCR in normal mucosa, but were significantly elevated after exposure to HCl, indicating that HCl causes production of PAF and expression of PAF receptors in esophageal mucosa and that PAF causes production of IL-6. PAF and IL-6, produced in the mucosa, are released to affect the circular muscle layer. In the circular muscle, PAF causes production of additional IL-6 that activates NADPH oxidase to induce production of H2O2. H2O2 causes formation of IL-1β that may induce production of PAF in the muscle, possibly closing a self-sustaining cycle of production of inflammatory mediators.


2003 ◽  
Vol 285 (6) ◽  
pp. G1129-G1138 ◽  
Author(s):  
Steven M. Miller ◽  
J. H. Szurszewski

The relationship between longitudinal and circular muscle tension in the mouse colon and mechanosensory excitatory synaptic input to neurons in the superior mesenteric ganglion (SMG) was investigated in vitro. Electrical activity was recorded intracellularly from SMG neurons, and muscle tension was simultaneously monitored in the longitudinal, circumferential, or both axes. Colonic intraluminal pressure and volume changes were also monitored simultaneously with muscle tension changes. The results showed that the frequency of fast excitatory postsynaptic potentials (fEPSPs) in SMG neurons increased when colonic muscle tension decreased, when the colon relaxed and refilled with fluid after contraction, and during receptive relaxation preceding spontaneous colonic contractions. In contrast, fEPSP frequency decreased when colonic muscle tension increased during spontaneous colonic contraction and emptying. Manual stretch of the colon wall to 10-15% beyond resting length in the circumferential axis of flat sheet preparations increased fEPSP frequency in SMG neurons, but stretch in the longitudinal axis to 15% beyond resting length in the same preparations did not. There was no increase in synaptic input when tubular colon segments were stretched in their long axes up to 20% beyond their resting length. The circumferential stretch-sensitive increase in the frequency of synaptic input to SMG neurons persisted when the colonic muscles were relaxed pharmacologically by nifedipine (2 μM) or nicardipine (3 μM). These results suggest that colonic mechanosensory afferent nerves projecting to the SMG function as length or stretch detectors in parallel to the circular muscle layer.


1996 ◽  
Vol 270 (3) ◽  
pp. E477-E482 ◽  
Author(s):  
J. W. Rhee ◽  
L. D. Longo ◽  
W. J. Pearce ◽  
N. H. Bae ◽  
G. J. Valenzuela ◽  
...  

Mechanisms involving the timing of normal parturition are not well understood in most animal species. To gain a greater understanding of the mechanisms, we employed hypoxia to perturb the normal system of parturition. The present study was designed to investigate the effects of chronic hypoxia on myometrial contractility in the near-term pregnant rat. Rats were exposed to room air (control) or to continuous hypoxia (10.5% O2) either from experimental days 19 through 21 (2-day exposure) or from experimental days 15 through 21 (6-day exposure). On day 21, blood was collected for hormone assays, and the uterine horns were collected from each dam. One horn was snap-frozen in liquid nitrogen for oxytocin (OT) receptor analysis, and the other was used for in vitro assessment of myometrial contractile responses to cumulative doses of OT or arginine vasopressin (AVP). Hypoxic exposure resulted in approximately 60% reduction of the maximal myometrial contractile response to OT and a significant reduction in OT binding sites from 256.9 +/- 34.9 to 84.9 +/- 21.3 fmol/mg protein (P<0.01). In contrast, the contractile response to AVP was unaffected after exposure to chronic hypoxia (P> 0.05). Additionally, we observed no difference in the plasma concentrations of estrogen, progesterone, and corticosterone. We conclude that chronic hypoxia decreased the effectiveness of OT-specific contractile mechanisms, at least partially through a decrease in OT binding sites.


2012 ◽  
Vol 79 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Romina Vargiu ◽  
Anna Perinu ◽  
Antonello De Lisa ◽  
Frank Tintrup ◽  
Francesco Manca ◽  
...  

Background Ureteral peristalsis is the result of coordinated mechanical motor performance of longitudinal and circular smooth muscle layer of the ureter wall. The main aim of this study was to characterize in smooth muscle of proximal segments of human ureter, the mechanical properties at level of muscle tissue and at level of myosin molecular motors. Methods Ureteral samples were collected from 15 patients, who underwent nephrectomy for renal cancer. Smooth muscle strips longitudinally and circularly oriented from proximal segments of human ureter were used for the in vitro experiments. Mechanical indices including the maximum unloaded shortening velocity (Vmax), and the maximum isometric tension (P0) normalized per cross-sectional area, were determined in vitro determined in electrically evoked contractions of longitudinal and circular smooth muscle strips. Myosin cross-bridge (CB) number per mm2 (Ψ) the elementary force per single CB (Ψ) and kinetic parameters were calculated in muscle strips, using Huxley's equations adapted to nonsarcomeric muscles. Results Longitudinal smooth muscle strips exhibited a significantly (p<0.05) faster Vmax (63%) and a higher P0 (40%), if compared to circular strips. Moreover, longitudinal muscle strips showed a significantly higher unitary force (Ψ) per CB. However, no significant differences were observed in CB number, the attachment (f1) and the detachment (g2) rate constants between longitudinal and circular muscle strips. Conclusions The main result obtained in the present work documents that the mechanical, energetic and unitary forces per CB of longitudinal layer of proximal ureter are better compared to the circular one; these preliminary findings suggested, unlike intestinal smooth muscle, a major role of longitudinal smooth muscle layer in the ureter peristalsis.


1991 ◽  
Vol 3 (2) ◽  
pp. 127 ◽  
Author(s):  
JM Wallace ◽  
R Helliwell ◽  
PJ Morgan

A highly specific oxytocin receptor ligand, 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH9(2)] vasotocin (125I-OTA), was used to localize high affinity oxytocin receptors in ovine uterine and oviduct tissues throughout the oestrous cycle. The pattern of binding revealed by in vitro autoradiography correlated well with the results of the homogenate receptor assays using the same ligand and with previous binding assays using the tritiated ligand. At oestrus, specific 125I-OTA binding was evident on the luminal epithelium of the caruncular and intercaruncular regions, on the epithelial cells lining the secretory uterine glands and in the stroma underlying the caruncular epithelium. In the myometrium diffuse labelling was evident in the outer longitudinal smooth muscle layer. At Day 4 of the cycle, binding to the stroma was diffuse and virtually absent from the glandular epithelium. No specific binding was evident in either tissue at Day 12 of the luteal phase, but by Day 14, prior to the decrease in peripheral progesterone concentrations, binding was again apparent on the luminal epithelium only. Specific binding to the oviduct was localized to the smooth muscle layer of the isthmus region of oestrous ewes and was not detected at any other stage of the oestrous cycle. These studies extend our knowledge of the distribution of oxytocin binding sites in uterine and oviduct tissues throughout the oestrous cycle and suggest that oxytocin has an important role in stimulating oviduct and uterine motility at a time crucial to successful egg collection and/or sperm embryo transport.


1975 ◽  
Vol 228 (6) ◽  
pp. 1887-1892 ◽  
Author(s):  
J Melville ◽  
E Macagno ◽  
J Christensen

The hypothesis examined was that contractions of the longitudinal muscle layer occurin the duodenum which are independent of those of the circular muscle layer and that they induce flow of duodenal contents. A segment of opossum duodenum isolated in vitro was marked and photographed during periods of longitudinal muscle contraction, when the circular muscle layer appeared inactive. The prequency of longitudinal oscillation of the marked points was 20.5 cycles/min. The longitudinal displacement wave spread caudad with an average velocity of 3.27 cm/s. Frequency and velocity of electrical slow waves were determined in similiar duodenal segments. Slow-wave frquencywas 18.9 cycles/min. In a two-dimensional mechanical model, flow induced by simulatedlongitudinal muscle layer appear to be driven by the electrical slow waves of the duodenum. They are capable of inducing a pattern of flow in which ocntents flow betweenthe core and the periphery of the intestinal conduit.


2001 ◽  
Vol 280 (4) ◽  
pp. G546-G554 ◽  
Author(s):  
Asensio Gonzalez ◽  
Sushil K. Sarna

The aim of this study was to investigate the modulation of in vitro rat colonic circular muscle contractions by dextran sodium sulfate (DSS)-induced inflammation and in spontaneous inflammation in HLA-B27 rats. We also examined the potential role of hydrogen peroxide (H2O2) in modulating excitation-contraction coupling. The muscle strips from the middle colon generated spontaneous phasic contractions and giant contractions (GCs), the proximal colon strips generated primarily phasic contractions, and the distal colon strips were mostly quiescent. The spontaneous phasic contractions and GCs were not affected by inflammation, but the response to ACh was suppressed in DSS-treated rats and in HLA-B27 rats. H2O2production was increased in the muscularis of the inflamed colon. Incubation of colonic muscle strips with H2O2suppressed the spontaneous phasic contractions and concentration and time dependently reduced the response to ACh; in the middle colon, it also increased the frequency of GCs. We conclude that H2O2mimics the suppression of the contractile response to ACh in inflammation. H2O2also selectively suppresses phasic contractions and increases the frequency of GCs, as found previously in inflamed dog and human colons.


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