Mechanisms underlying the prokinetic effects of endogenous glucagon-like peptide-1 in the rat proximal colon

Glucagon-like peptide-1 (GLP-1), a well-known insulin secretagogue, is released from enteroendocrine L cells both luminally and basolaterally to exert different effects. Basolaterally released GLP-1 increases epithelial ion transport by activating CGRP-containing enteric afferent neurons. Although bath-applied GLP-1 reduced the contractility of colonic segments, GLP-1-induced stimulation of afferent neurons could also accelerate peristaltic contractions. Here, the roles of endogenous GLP-1 in regulating colonic peristalsis were investigated using isolated colonic segments. Isolated segments of rat proximal colon were placed in an organ bath, serosally perfused with oxygenated physiological salt solution and luminally perfused with degassed 0.9% saline. Colonic wall motion was recorded using a video camera and converted into spatio-temporal maps. Intraluminal administration of GLP-1 (100 nM) stimulating the secretion of GLP-1 from L cells increased the frequency of oro-aboral propagating peristaltic contractions. The acceleratory effect of GLP-1 was blocked by luminally-applied exendin-3 (9-39) (100 nM), a GLP-1 receptor antagonist. GLP-1-induced acceleration of peristaltic contractions was also prevented by bath-applied BIBN4069 (1 μM), a CGRP receptor antagonist. In colonic segments that had been exposed to bath-applied capsaicin (100 nM) that desensitizes extrinsic afferents, GLP-1 was still capable of exerting its prokinetic effect. Stimulation of endogenous GLP-1 secretion with a luminally-applied cocktail of short-chain fatty acids (1 mM) increased the frequency of peristaltic waves in an exendin-3 (9-39)-sensitive manner. Thus, GLP-1 activates CGRP-expressing intrinsic afferents to accelerate peristalsis in the proximal colon. Short-chain fatty acids appear to stimulate endogenous GLP-1 secretion from L cells resulting in the acceleration of colonic peristalsis.

Ascension of Chlamydia is moderated by uterine peristalsis and the neutrophil response to infection

Chlamydia trachomatis is a common sexually transmitted infection that is associated with a range of serious reproductive tract sequelae including in women Pelvic Inflammatory Disease (PID), tubal factor infertility, and ectopic pregnancy. Ascension of the pathogen beyond the cervix and into the upper reproductive tract is thought to be necessary for these pathologies. However, Chlamydia trachomatis does not encode a mechanism for movement on its genome, and so the processes that facilitate ascension have not been elucidated. Here, we evaluate the factors that may influence chlamydial ascension in women. We constructed a mathematical model based on a set of stochastic dynamics to elucidate the moderating factors that might influence ascension of infections in the first month of an infection. In the simulations conducted from the stochastic model, 36% of infections ascended, but only 9% had more than 1000 bacteria ascend. The results of the simulations indicated that infectious load and the peristaltic contractions moderate ascension and are inter-related in impact. Smaller initial loads were much more likely to ascend. Ascension was found to be dependent on the neutrophil response. Overall, our results indicate that infectious load, menstrual cycle timing, and the neutrophil response are critical factors in chlamydial ascension in women.

411 Sperm movement, storage, and release from the oviduct

After semen deposition, a fraction of sperm is transported through the female reproductive tract to the lower oviduct, the isthmus, where sperm are retained to form a reservoir. Some of these sperm are released to move to the upper oviduct, the site of fertilization. For sperm to make this journey, they must overcome challenges including possible phagocytosis, high fluid viscosity, and peristaltic contractions of the tract. The study of sperm transport is complex because so few sperm reach the site of fertilization. We have focused our studies on how sperm are retained in the reservoir, how storage prolongs sperm lifespan, and how sperm are released to fertilize oocytes. Sperm storage is particularly important in situations in which ovulation is not tightly synchronized with semen deposition. This occurs in domestic animals, but is especially notable in some species of bats, birds, and insects. Using porcine sperm and an array of 400 common glycans, we identified two specific glycan motifs found in all structures that bound sperm, a Lewis X trisaccharide and a branched 6-sialylated oligosaccharide. Tandem MS profiling indicated that both motifs were abundant in the asparagine-linked glycans of the oviduct epithelium and several larger oligosaccharides were identified that contained both motifs. When these motifs were immobilized, each could retain sperm, suppress Ca2+ influx and lengthen sperm lifespan. Secretions from the cumulus-oocyte complex (COC) and progesterone released sperm from immobilized oviduct glycans, suggesting that COCs can themselves signal sperm release. Progesterone-induced release required CatSper channels, sperm hyperactivation and was dependent on sperm protein degradation. These studies support a model in which sperm are retained in the isthmus by specific glycans on the epithelium, which extends sperm lifespan until COCs produce releasing factors that promote sperm liberation from the isthmus and movement to the ampulla to fertilize the COCs.

The Distribution and Possible Roles of Small Cardioactive Peptide in the Nudibranch Melibe leonina

Synopsis The neuropeptide small cardioactive peptide (SCP) plays an integrative role in exciting various motor programs involved in feeding and locomotion in a number of gastropod species. In this study, immunohistochemistry, using monoclonal antibodies against SCPB, was used to localize SCPB-like-immunoreactive neurons in the central nervous system, and map their connections to various tissues, in the nudibranch, Melibe leonina. Approximately 28–36 SCPB-like-immunoreactive neurons were identified in the M. leonina brain, as well as one large neuron in each of the buccal ganglia. The neuropil of the pedal ganglia contained the most SCPB-like-immunoreactive varicosities, although only a small portion of these were due to SCPB-like-immunoreactive neurons in the same ganglion. This suggests that much of the SCPB-like immunoreactivity in the neuropil of the pedal ganglia was from neurons in other ganglia that projected through the pedal–pedal connectives or the connectives from the cerebral and pleural ganglia. We also observed extensive SCPB innervation along the length of the esophagus. Therefore, we investigated the impact of SCPB on locomotion in intact animals, as well as peristaltic contractions of the isolated esophagus. Injection of intact animals with SCPB at night led to a significant increase in crawling and swimming, compared to control animals injected with saline. Furthermore, perfusion of isolated brains with SCPB initiated expression of the swim motor program. Application of SCPB to the isolated quiescent esophagus initiated rhythmic peristaltic contractions, and this occurred in preparations both with and without the buccal ganglia being attached. All these data, taken together, suggest that SCPB could be released at night to arouse animals and enhance the expression of both feeding and swimming motor programs in M. leonina.

Solute and water transport along an inner medullary collecting duct undergoing peristaltic contractions

The mechanism by which solutes accumulate in the inner medulla of the mammalian kidney has remained incompletely understood. That persistent mystery has led to hypotheses based on the peristaltic contractions of the pelvic wall smooth muscles. It has been demonstrated the peristaltic contractions propel fluid down the collecting duct in boluses. In antidiuresis, boluses are sufficiently short that collecting ducts may be collapsed most of the time. In this study, we investigated the mechanism by which about half of the bolus volume is reabsorbed into the collecting duct cells despite the short contact time. To accomplish this, we developed a dynamic mathematical model of solute and water transport along a collecting duct of a rat papilla undergoing peristaltic contractions. The model predicts that, given preexisting axial concentration gradients along the loops of Henle, ∼40% of the bolus volume is reabsorbed as the bolus flows down the inner medullary collecting duct. Additionally, simulation results suggest that while the contraction-induced luminal hydrostatic pressure facilitates water extraction from the bolus, that pressure is not necessary to concentrate the bolus. Also, neither the negative interstitial pressure generated during the relaxation phase nor the concentrating effect of hyaluronic acid has a significant effect on bolus concentration. Taken together, these findings indicate that the high collecting duct apical water permeability allows a substantial amount of water to be extracted from the bolus, despite its short transit time. However, the potential role of the peristaltic waves in the urine-concentrating mechanism remains to be revealed.

Quantification of gastric emptying caused by impaired coordination of pyloric closure with antral contraction: a simulation study

Proper coordination of gastric motor functions is required for healthy gastric emptying. However, pyloric function may be impaired by functional disorders or surgical procedures. Here, we show how coordination between pyloric closure and antral contraction affects the emptying of liquid contents. We numerically simulated fluid dynamics using an anatomically realistic gastrointestinal geometry. Peristaltic contractions in the proximal stomach resulted in gastric emptying at a rate of 3–8 ml min −1 . When the pylorus was unable to close, the emptying rate increased to 10–30 ml min −1 , and instantaneous retrograde flow from the duodenum to the antrum occurred during antral relaxation. Rapid emptying occurred if the pylorus began to open during the terminal antral contraction, and the emptying rate was negative if the pylorus only opened during the antral relaxation phase. Our results showed that impaired coordination between antral contraction and pyloric closure can result in delayed gastric emptying, rapid gastric emptying and bile reflux.

Fatty acid bioaccessibility and structural breakdown from in vitro digestion of almond particles

In vitro gastric digestion of almond particles using a model with simulated peristaltic contractions resulted in particle size reduction and higher fatty acid bioaccessibility than in vitro digestion using a model that lacked peristaltic contractions.