Enteric-endocrine system

It has been known for some time that the enteric nervous system does not simply regulate smooth muscle contraction, but is intimately involved in the control of transport processes in enterocytes. Nerve fibres in the mucosa terminate subjacent to the basement membrane of epithelial and entero-endocrine cells, on which muscarinic acetylcholine receptors (mAChRs)... 

The GI system is responsible at its most basic level for providing a continual supply of water, electrolytes, minerals, and nutrients. This is achieved by a myriad of specialized cells and coordinated interplay of motility, secretion, digestion, absorption, blood flow, and lymph flow. These components are under elaborate control of the central and enteric nervous systems, endocrine and paracrine regulation of hormones. The highly complex nature of GI function is clearly illustrated by the estimate that 80 to 100 million neurons exist within the enteric nervous system, a number comparable to that found within the spinal column, hence described as a "second brain."171... 

The three targets that are the first point of contact between environmental chemicals and the body will be discussed first the gastrointestinal tract, the respiratory system, and the skin. Recall from Chapter 2 that chemicals enter the blood after absorption, so this fluid is the next target (see Figure 2.1). Then come the liver, the kidneys, and the nervous system. The chapter concludes with a discussion of some chemicals that can damage the reproductive system and some that can cause birth defects, the so-called teratogens, and other forms of developmental toxicity. Brief discussions of immune system, cardiovascular system, muscle, and endocrine system toxicities are also offered. 

The gastrointestinal system of zebrafish presents clear differences from the human system. The zebrafish does not possess a stomach, the intestine is continuous with the pharynx through a short esophagus, and no sphincters are present [61]. However, zebrafish have most of the cell types observed in the small intestine -absorptive, endocrine, goblet, and interstitial cells of Cajal, although Paneth cells are absent. Gut contractions are under the control of the enteric nervous systems, which respond to different pharmaceuticals in similar way as the mammalian counterpart. For example, zebrafish embryos can be used as predictor of emetic response to pharmaceuticals, one of the most commonly reported clinical adverse effects to be considered in the development of new dmgs [61]. 

As stated earlier, the annual cycles of species and populations divide into periods. The overall description would be the syndrome of the population, while individual metabolic characteristics would be symptoms , borrowing terms from the medical profession. Each period manifests a specific set of metabolic features which support the normal course of vital processes in the population, and the population would enter the next period of the cycle only if the preceding step had been completed. If it had not, the situation would lead to that mass mortality which is so common in nature. The change in metabolism is triggered with the help of the endocrine system, as will be described in the next section. 

The gut contains a collection of nerves called the enteric nervous system. Various activities of the gut, such as peristaltic contractions, and certain activities of the pancreas and gall bladder, are controlled in a manner that is relatively independent of the central nervous system. The central nervous system consists of the brain and spinal cord. Five type,s of activity are controlled by the enteric nervous system (1) contraction of smooth muscles that create the peristaltic waves used to mix and propel food through the intestines (2) release of juices by secretory cells (5) release of hormones from endocrine ceils of the gut (4) patterns of blood flow through the arteries of the gut (variations in blood flow occur because of the opening of blood vessels (vasodilation) or the dosing of blood vessels (vasoconstriction)] and (5) activities of immune cells of the gut (GoyaI and Hirano, 1996). 

Dioxin, PCB, DDT, and the like, i.e., chlorinated aromatic hydrocarbons are believed to bind to a special receptor called AH receptor (AH stands for aryl hydrocarbon). The AH receptor bound with dioxin (or PCB) enters into the nucleus of the cell, and binds to a specific site of a DNA. One of the effects caused by such a binding seems to be an induction of an enzyme dependent on cytochrome P-450. Cytochrome P-450-dependent monooxygenase was talked about in Sect. 6.2.2, and is involved in the metabolism of a wide variety of compounds including steroids and foreign substances (drugs). Probably the P-450 enzymes induced by dioxin, PCB, and others would then metabolize steroid hormones unnecessarily, and thus disrupt the endocrine system. The details are still not very well understood. However, you see that the processes are all chemical reactions at the deepest level. 

An illustration of the regions of regulation of gastric add secretion, divided into central dorsal motor nucleus, enteric nervous system, neural, endocrine, and paracrine. Impulses flow down the vagus from the dorsal motor nucleus to the enteric nervous system in the wall of the stomach. From there, acetylcholine is released to the G cell, D cell, and parietal cell and PACAP to the ECL cell. 

Acetylcholine is released from the postganglionic fibers of the enteric nervous system and regulates gastric acid secretion both by directly acting on the parietal cell and indirectly stimulating several endocrine cells, which in turn modulate the activity of the parietal cell [6]. Five subtypes of the... 

Endocrine system. Lanthanum binds to the cell surface of parathyroid cells (without entering the cells), but this gives rise to increased Ca permeability resulting in a rise in intracellular Ca (Gylfe, Larsson et al. 1986). Parathyroid hormone (PTH) release from the gland is normally inhibited by Ca but is inhibited by lanthanum to an even greater extent. Incubation of parathyroid cells with pertussis toxin, a G-protein inactivator that blocks inhibition by Ca, does not block the inhibition of PTH release by lanthanum. There may be two cell surface sites that recognize lanthanmn and Ca independently (Fitzpatrick 1990).. 

Stress can be defined as the physiological reaction of an organism to external or internal stimuli in which the body initiates various defense mechanisms to maintain homeostasis (Ramsey 1982 Cruz et al. 2012). The stress response involves a complex network of mechanisms essential for survival, mediated by neurotransmitters, peptidic hormones, and endocrine hormones from the enteric nervous system (ENS). These molecules modulate the humoral and cellular components of the intestinal immune system (de Jonge 2013). 

As PCB production increased, more concerns were raised about the health and environmental effects of PCBs, which entered the environment through leakage, production processes, and improper disposal. The persistence and lipophilicity of PCBs resulted in its biomagnification in the environment (see DDT). Problems associated with PCB contamination in wildlife include deformities, tumors, disruption in the endocrine and reproduction systems, and death. Human exposure to PCBs occurs through environmental and occupational routes. The primary exposure... 

Fig. 15. Hypothetical model of how initiators and modulators that affect insulin release may reach A-, B- and D-cells. The first target of arterial blood containing nutrients, hormones, peptides and drugs is the B-cell. From there, via an intraislet portal vein system, blood which now also contains released insulin flows to the mantle where A- and D-cells are localized and from there enters the circulation. Nerves derived from the autonomous nervous system which contain neurotransmitters (acetylcholine, noradrenaline) and neuropeptides (including vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), galanin) are connected to islet cells. Glucagon (A-cells) and somatostatin (D-cells) reach other endocrine cells in the islet in a paracrine manner. The B-cell may also be the target of previously released insulin via a short loop.

At moderate concentrations, TNFa enters the blood stream where it can act as an endocrine factor. The principal systemic actions of TNFs include ... 

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