Feeding ruminants a reduced N diet is a common approach to reduce N output based on rumino-hepatic circulation. However, a reduction in N intake caused massive changes in Ca and inorganic phosphate (P i ) homoeostasis in goats. Although a single dietary Ca reduction stimulated intestinal Ca absorption in a calcitriol-dependent manner, a concomitant reduction of Ca and N supply led to a decrease in calcitriol, and therefore a modulation of intestinal Ca and P i absorption. The aim of this study was to examine the potential effects of dietary N or Ca reduction separately on intestinal Ca and P i transport in young goats. Animals were allocated to a control, N-reduced, Ca-reduced or combined N-and Ca-reduced diet for about 6 − 8 weeks, whereby N content was reduced by 25 % compared with recommendations. In Ussing chamber experiments, intestinal Ca flux rates significantly decreased in goats fed a reduced N diet, whereas P i flux rates were unaffected. In contrast, a dietary Ca reduction stimulated Ca flux rates and decreased P i flux rates. The combined dietary N and Ca reduction withdrew the stimulating effect of dietary Ca reduction on Ca flux rates. The expression of Ca-transporting proteins decreased with a reduced N diet too, whereas P i -transporting proteins were unaffected. In conclusion, a dietary N reduction decreased intestinal Ca transport by diminishing Ca-transporting proteins, which became clear during simultaneous N and Ca reduction. Therefore, N supply in young ruminant nutrition is of special concern for intestinal Ca transport.Key words: Flux rates of calcium and phosphate: Goats: Na + -dependent P i transporter IIb: Transient receptor potential vanilloid channel type 6: Ussing chambersFeeding ruminants a N-reduced diet is preferable for economic and environmental reasons. Dietary crude protein (CP) concentrations of 11 − 12 % were recommended to meet the requirements of growing goats (1) . A reduced dietary N supply was associated with a significant reduction in urinary N excretion (2) due to increased expression of renal urea transporters, and thus greater renal urea re-absorption (3) in goats. In addition, the urea transporting capacity of the ruminal epithelium was increased due to dietary N reduction (4) . By possessing such efficient recycling mechanisms, ruminants such as goats are able to maintain rumen microbes' N supply, and therefore a sufficient synthesis of microbial protein as the most important source for host protein, provided that energy supply to the rumen flora is also adequate for microbial protein synthesis.As monogastric species do not have the similar potential to utilise N efficiently, a low-protein diet changes metabolic pathways seriously. A reduction of dietary protein leads to changes in Ca and inorganic phosphate (P i ) homoeostasis in monogastric animals and humans, including decrease in intestinal Ca absorption, reduced urinary Ca excretion and diminished plasma calcitriol and insulin-like growth factor 1 (IGF1) concentrations (5)(6)(7)(8) .Despite the N-rec...

The pig is commonly believed to be a relevant model for human gut functions-however, there are only a few comparative studies and none on neural control mechanisms. To address this lack we identified as one central aspect mechanosensitive enteric neurons (MEN) in porcine and human colon. We used neuroimaging techniques to record responses to tensile or compressive forces in submucous neurons. Compression and stretch caused Ca-transients and immediate spike discharge in 5-11% of porcine and 15-24% of human enteric neurons. The majority of these MEN exclusively responded to either stimulus quality but about 9% responded to both. Most of the MEN expressed choline acetyltransferase and substance P; nitric oxide synthase-positive MEN primarily occurred in distal colon. The findings reveal common features of MEN in human and pig colon which we interpret as a result of species-independent evolutionary conservation rather than a specific functional proximity between the two species. The enteric nervous system (ENS), which is integrated into the wall of the gastrointestinal tract (GIT) from the oesophagus to the anal sphincter, enables the GIT to generate reflex activity independent from central influences 1-3. The ENS is organized in two complex neuronal networks called the submucosal plexus (SMP) and the myenteric plexus (MP). In both, the pig and human the SMP consists of two layers interconnected by interganglionic nerve fiber tracts 4,5. The SMP regulates mostly epithelial functions, such as secretion and absorption, as well as blood flow, cell proliferation and immune responses. The distinct parts of the SMP are called inner SMP (ISMP) and outer SMP (OSMP) with the ISMP being located closely to the lamina muscularis mucosae, whereas the OSMP is located on the luminal side of the circular muscle layer 6. In the porcine and human colon mainly neurons in the ISMP predominantly project to the mucosa 7-9 , and hence likely regulate epithelial functions 10. Enteric neurons can be activated by various stimuli, including chemical stimuli as well as mechanical distortion 11-17. During muscle contraction and relaxation enteric neurons are constantly exposed to distorting forces 16,18. Remarkably, even enteric neurons classically defined as interneurons or motoneurons are mechanosensitive, suggesting that mechanosensitive enteric neurons (MEN) are multifunctional 14,15,19. With intracellular recording techniques it has been shown that MEN in the MP respond to distension as well as to mucosal distortion 20-22. An important step forward was the use of imaging techniques, as they allowed to record simultaneously from a larger set of neurons and were also a prerequisite to study enteric neurons in larger animals 14-17,23,24. Using von Frey hair probing and intraganglionic volume injection, compression sensitive MEN have been identified in the MP of the guinea pig gastric corpus, ileum and colon 14,16,23 as well as in mouse ileum and colon 15. Furthermore, von Frey hair probing was used to identify compression sensitive MEN in isol...

Neurons of the enteric submucous plexus are challenged by osmolar fluctuations during digestion and absorption of nutrients. r Central neurons are very sensitive to changes in osmolality but knowledge on that issue related to enteric neurons is sparse. r The present study focuses on investigation of osmosensitivity of submucosal neurons including potential molecular mediating mechanisms. r Results show that submucosal neurons respond to hypoosmolar stimuli with increased activity which is partially mediated by the transient receptor potential vanilloid 4 channel. r We provided important information on osmosensitive properties of enteric neurons. These data are fundamental to better explain the nerve-mediated control of the gastrointestinal functions during physiological and pathophysiological (diarrhoea) conditions.

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In ruminants, a decrease of dietary nitrogen (N) is an appropriate feeding concept to reduce environmental pollution and costs. In our previous study, when goats were kept on an N-reduced diet, a decrease of plasma urea concentration and an increase of renal urea transporters were demonstrated. Renal urea absorption plays a crucial role for renal water absorption and urine concentration. Renal collecting duct water absorption is mainly mediated by the water channel aquaporin 1 and 2 (AQP1 and AQP2). Therefore, the aim of the present study was to investigate the effects of a dietary N reduction on expression of renal AQP1 and AQP2 in young goats. Twenty male White Saanen goats, 3 months old, were divided equally into two feeding groups, receiving either a diet with an adequate or a reduced-N supply. Goats fed a reduced-N diet showed significantly higher amounts of AQP1 mRNA in cortical tissue, and the expression of AQP2 mRNA and protein were highly elevated in renal outer medulla. An increase of vasopressin concentrations in plasma were detected for the N-reduced fed goats. Therefore, a stimulation of renal water absorption can be assumed. This might be an advantage for ruminants in times of N reduction due to higher urea concentrations in the tubular fluid and which might result in higher absorption of urea by renal urea transporters. Therefore, interplay of aquaporin water channels and urea transporters in the kidney may occur to maintain urea metabolism in times of N scarcity in young goats.