Urocortins and the regulation of gastrointestinal motor function and visceral pain

Urocortin (Ucn) 1, 2 and 3 are corticotropin-releasing factor (CRF)-related peptides recently characterized in mammals. Urocortin 1 binds with high affinity to CRF type 1 (CRF1) and type 2 (CRF2) receptors while Ucn 2 and Ucn 3 are selective CRF2 ligands. They also have a distinct pattern of distribution, both in the brain and the gastrointestinal tract, compatible with a role mediating, with CRF, the response to stress. In rats and mice, Ucn 1 injected centrally or peripherally inhibited gastric emptying and stimulated colonic propulsive motor function, mimicking the effects of stress or exogenous CRF. Centrally administered Ucn 2 inhibited gastric emptying with similar potency as CRF, while Ucn 1 and Ucn 3 were less potent. However, after peripheral administration, Ucn 1 and Ucn 2 were more potent than CRF. In mice, centrally administered Ucn 1 and 2 stimulated colonic motility with lower potency than CRF, and Ucn 3 was inactive. Studies with selective CRF1 and CRF2 antagonists demonstrated that the gastric-inhibitory and colonic-stimulatory effects of exogenously administered Ucns are mediated through CRF2 and CRF1 receptors, respectively. In addition, Ucn 2 showed visceral anti-nociceptive activity associated with the selective activation of CRF2 receptors. These observations suggest that, acting centrally and peripherally, Ucns might play a significant role in the modulation of gastrointestinal motor and pain responses during stress and stress-related pathophysiological conditions.     

Characteristics of the motor function of the proximal segment of the gastrointestinal tract

Dynamics of the solid carbohydrate food evacuation from the duodenum has been determined in chronic experiments on dogs using modified technique for multiple drainage of intestinal fistulas. It is established that dynamics of the duodenal chyme emptying depends on the absolute quantity of the stomach-evacuated food and includes three phases: increase in the evacuation rate, exponential phase and that of accelerated evacuation. The highest rate of the duodenal contents is observed in the period from the 90th to 210th minute after food intake, the lowest one--at the end of the digestive cycle. A conclusion is made concerning the high degree of coordination of the evacuatory stomach and duodenum function.     

The structural organization and neurochemical mechanisms of the participation of the nucleus accumbens in the interaction of the limbic and motor systems and in the regulation of motor behavior]

The review of own and literature data devoted to structural and neurochemical organization of the nucleus accumbens (Acc) as well as spatial organization of their projection fibers in comparison with nucleus caudatus (neostriatum) has been presented. The facts concerned with correlations revealed between both the cell clusters and histochemical compartments as well as the compartmental organization of afferent and efferent striatal connections were analyzed. The presented data propose the existence of sensorimotor and limbic parts of the dorsal and ventral striatum, which are involved in the parallelly functioning systems. The common and different signs of these two systems and its role in the regulation of the movement behaviour has been proposed. A lot of attention also was payed to the Acc and the neostriatum interaction. The many pathways by which Acc can influence neostriatum functions and therefore the motor activity controlled by the neostriatum are discussed. It was shown that the Acc can influence on the striatal synaptic DA release. The sign of this influence depended upon DA/glutamic acid interactions in the Acc. It was stressed that the influence of Acc on striatal DA-ergic system is very likely mediated via kainate/quisqualate (but not NMDA) inputs of the neostriatum. The balance of DA-ergic mechanisms of neostriatum and Acc as important basis of animals adequate behaviour in conditioning situation was proposed. The disbalance of these mechanisms could leads to pathology.     

Hormonal regulation of the fish gastrointestinal tract

The gastrointestinal tracts (GIT) of fish and other vertebrates are challenged with a diversity of functional demands caused by changes and differences in dietary inputs and environmental conditions. This contribution reviews how hormonal regulation plays an essential role in modulating the GIT functions of fish to match changes in functional demands. Exemplary is how hormones produced by the GIT, the associated organs (e.g., pancreas), and other sources (e.g., hypothalamus, adrenal cortex, thyroid, gonads) modulate the digestive processes (motility, secretion, and nutrient absorption) in response to dietary inputs. Hormones regulate the other GIT functions of osmoregulation (secretion and absorption of electrolytes and water), immunity, endocrine secretions, metabolism, and the elimination of toxic metabolites and environmental contaminants to match changes in environmental conditions and physiological states. Although the regulatory molecules and associated signaling pathways have been conserved during evolution of the vertebrate GIT, the specific responses often vary among fish with different feeding habits and from different environments, and can differ from those described for mammals.     

Neuronal correlates of the motor function of the cerebral motor cortex

Modern ideas about the motor cortex neuronal mechanisms ensuring the initiation and correction of the instrumental manipulational movements in mammals have been analysed. A close correlation has been established to exist between the neuronal activity and various characteristics of movement including those that are not induced by muscle force. The role of somatic afferentation in the formation and realization of the movement programme is analysed as well as in motor output modulation by means of fast feedback.     

Distribution and function of monoacylglycerol lipase in the gastrointestinal tract

The endogenous cannabinoid system plays an important role in the regulation of gastrointestinal function in health and disease. Endocannabinoid levels are regulated by catabolic enzymes. Here, we describe the presence and localization of monoacylglycerol lipase (MGL), the major enzyme responsible for the degradation of 2-arachidonoylglycerol. We used molecular, biochemical, immunohistochemical, and functional assays to characterize the distribution and activity of MGL. MGL mRNA was present in rat ileum throughout the wall of the gut. MGL protein was distributed in the muscle and mucosal layers of the ileum and in the duodenum, proximal colon, and distal colon. We observed MGL expression in nerve cell bodies and nerve fibers of the enteric nervous system. There was extensive colocalization of MGL with PGP 9.5 and calretinin-immunoreactive neurons, but not with nitric oxide synthase. MGL was also present in the epithelium and was highly expressed in the small intestine. Enzyme activity levels were highest in the duodenum and decreased along the gut with lowest levels in the distal colon. We observed both soluble and membrane-associated enzyme activities. The MGL inhibitor URB602 significantly inhibited whole gut transit in mice, an action that was abolished in cannabinoid 1 receptor-deficient mice. In conclusion, MGL is localized in the enteric nervous system where endocannabinoids regulate intestinal motility. MGL is highly expressed in the epithelium, where this enzyme may have digestive or other functions yet to be determined.     

Possible mechanisms of amygdala participation in the regulation of gastric motor activity

Mechanisms of the amygdala central nucleus (CNA) influence on gastric motor reflex activity were studied in electrophysiological and neuroanatomical experiments in Wistar rats. In the anaesthetized animals, electrical stimulation of the CNA affected spontaneous gastric motility and caused inhibitory as well as excitatory changes of vagus-induced gastric relaxation. The most significant and mainly inhibitory effects were observed under the stimulation of the medial CNA. Microinjection of the anterograde tracer Phaseolus vulgaris-leucoagglutimn (PHA-L) into the different divisions of the CNA revealed direct projections from its dorso-medial portion to the gastric related area of the dorsal vagal complex. Electrical stimulation of this amygdaloid area was found to change activity of the bulbar gastric related neurons. Inhibitory and excitatory changes of their vagus-induced responses under the amigdala stimulation were manifested as a general modulation of all phases of the reaction or a selective modulation of some of them. These mechanisms may underlie the amygdalo-fugal modulation of gastric motor reflex activity.     

Orexin与胃肠活动的调节

Orexin除了主要分布于中枢神经系统的下丘脑外,还广泛分布于包括外周的胃肠组织,如胃肠神经丛和内分泌细胞等部位。Orexin在促进食欲的同时,还能通过中枢和外周途径调节胃肠运动和消化液的分泌。     

Involvement of rabbit motor cortex neurons in the instrumental behavior before and after chronic ethanol consumption: a comparison with the limbic cortex

The effect of acute administration is significantly more prominent in the limbic (cingulate) than in the motor cortex [9]. We proposed that the limbic cortex is more sensitive also to chronic ethanol treatment (CET). It was shown that morphology as well as neuronal activity of the limbic cortex changed greatly after the CET [7]. The missing link of testing the above proposition was a comparison of the obtained data with the results of the experimental study of CET influence on the motor cortex. Morphology of the anterolateral motor cortex and activity of its neurons in the instrumental food-acquisition behavior were studied in 6 male rabbits after CET (9 months). It was found that the limbic cortex was modified morphologically and functionally to a significantly greater extent than the motor cortex. We consider the fact that in the limbic cortex of a healthy individual there are many neurons, which for a while cease their discharges after the acute ethanol administration, to be among the most important reasons for this difference. Such-like repeated activity interruptions in the course of CET impair the performance of the systems incorporating these neurons. In such a way ethanol prevents all neurons, especially the mentioned ones, from receiving adequate metabolic supply that is necessary for their survival and functioning.