Gastrointestinal tract enteric nervous system

Atropine and scopolamine have antispasmodic effects on the gastrointestinal tract. It partly inhibits vagal influence in the gut, reducing motility. However, the enteric nervous system also employs serotonin and dopamine, so parasympathetic innervation plays a modulatory role. 

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. 

Brain serotonergic neurons are involved in numerous diffuse functions such as mood, sleep, appetite, and temperature regulation, as well as the perception of pain, the regulation of blood pressure, and vomiting (see Chapter 21). Serotonin also appears to be involved in clinical conditions such as depression, anxiety, and migraine. Serotonergic neurons are also found in the enteric nervous system of the gastrointestinal tract and around blood vessels. In rodents (but not in humans), serotonin is found in mast cells. 

HT3 receptors in the gastrointestinal tract and in the vomiting center of the medulla participate in the vomiting reflex (see Chapter 62). They are particularly important in vomiting caused by chemical triggers such as cancer chemotherapy drugs. 5-HTip and 5-HT4 receptors also play important roles in enteric nervous system function. 

Substance P is present in the central nervous system, where it is a neurotransmitter (see Chapter 21), and in the gastrointestinal tract, where it may play a role as a transmitter in the enteric nervous system and as a local hormone (see Chapter 6). 

Alosetron is a potent and selective 5-HT3 receptor antagonist. 5-HT3 receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. 5-HT3 receptor antagonists such as alosetron inhibit activation of these channels that results in the modulation of the enteric nervous system. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions, processes that relate to the pathophysiology of IBS. 

The gastrointestinal (GI) tract is in a continuous contractile, absorptive, and secretory state. The control of this state is complex, with contributions by the muscle itself, local nerves (i.e., the enteric nervous system, ENS), the central nervous system (CNS), and humoral pathways. Of these, perhaps the most important regulator of physiological gut function is the ENS (Figure 37-1), which is an autonomous collection of nerves within the wall of the Gl tract, organized into two connected networks of neurons the myenteric (Auerbach s) plexus, found between the circular and longitudinal muscle layers, and the submucosal (Meissner s) plexus, found below the epithehum. The former is responsible for motor control, while the latter regulates secretion, fluid transport, and vascular flow. 

A. Anatomic Aspects of the ANS The motor (efferent) portion of the ANS is the major pathway for information transmission from the central nervous system (CNS) to the involuntary effector tissues (smooth muscle, cardiac muscle, and exocrine glands Figure 6-1). The enteric nervous system (ENS) is a semiautonomous part of the ANS, with specific functions for the control of the gastrointestinal tract. The ENS consists of the myenteric plexus (plexus of Auerbach) and the submucous plexus (plexus of Meissner) and includes inputs from the parasympathetic and sympathetic nervous systems. 

Gastrointestinal tract The gastrointestinal tract is well endowed with both alpha and beta receptors, located on both smooth muscle and on neurons of the enteric nervous system. Activation of either alpha or beta receptors leads to relaxation of the smooth muscle. Alpha2 agonists may decrease salt and water secretion into the intestine. 

Costa M, Furness JB, Llewellyn-Smith IJ. Histochemistry of the enteric nervous system. In Johnson LR, ed. Physiology of the gastrointestinal tract, 2nd ed., vol. 1. New York Raven Press, 1987 1. 

The autonomic nervous system is divided into the sympathetic and parasympathetic components, which typically exert opposing effects. The sympathetic system is involved in the fight or flight reaction (increased blood pressure and heart rate, and accommodation for increased vision, for example) that prepares the organism for stressful situations. The parasympathetic system conversely establishes a more relaxed situation, for instance, the rest period after a meal. The autonomic nervous system that is responsible for the independent control of the mechanical and secretory functions of the gastrointestinal tract is sometimes called the enteric system. 

HT3 receptors in the gastrointestinal tract activate visceral afferent pain sensation via extrinsic sensory neurons from the gut to the spinal cord and central nervous system. Inhibition of afferent gastrointestinal 5-HT3 receptors may inhibit unpleasant visceral afferent sensation, including nausea, bloating, and pain. Blockade of central 5-HT3 receptors also reduces the central response to visceral afferent stimulation. In addition, 5-HT3-receptor blockade on the terminals of enteric cholinergic neurons inhibits colonic motility, especially in the left colon, increasing total colonic transit time. 

Metaldehyde is readily absorbed from the gastrointestinal tract. Metaldehyde s primary decomposition product in the body is acetaldehyde. Metabolites can cross the blood-brain barrier and enter the central nervous system. 

When a drug is administered, it does not achieve an equal concentration throughout the body. Unless a drug is injected directly into the blood stream it will be absorbed from its site of administration, then enter the systemic circulation and be transported to the tissues in plasma. The body can be considered to be made up of aqueous and lipid compartments. Lipid compartments include all cell membranes and adipose tissue. Aqueous compartments include tissue fluid, cellular fluid, blood plasma and fluid in places like the central nervous system, the lymphatic system, joints and the gastrointestinal tract. The distribution of a drug into these different compartments depends on many factors. 

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