Gastrointestinal function motility

In the periphery, 5-HT4 receptor mRNA is found in vascular smooth muscle. Newly developed drugs that activate 5-HT4 receptors are of interest for their potential in treating cardiac arrhythmia. The 5-HT4 receptor is also located on neurons of the alimentary tract, for example the myenteric plexus of the ileum, and on smooth muscle cells and secretory cells of the gastrointestinal tract, where they evoke secretions and the peristaltic reflex. 5-HT4 receptor agonists (e.g. cisapride, prucalopride, tegaserod) are used therapeutically in the treatment of constipation-predominant irritable bowel syndrome and in functional motility disorders of the upper gastrointestinal tract. 

FIGURE 5—59. Peripheral 5HT3 and 5HT4 receptors in the gut may regulate appetite as well as other gastrointestinal functions, such as gastrointestinal motility. 

Experiments carried out in the conscious rat demonstrated that H3 receptors contribute only to the central, and not the peripheral, regulation of intestinal motility (Fargeas et al., 1989). In addition, the concomitant ineffectiveness on acid secretion of peripherally administered H3 ligands seems to exclude a significant role of H3 receptors in the peripheral regulation of gastrointestinal functions. Lastly, in the mouse H3 receptors do not seem to have any appreaciable influence on gastrointestinal motility (Oishi et al., 1993)... 

Lung Eye Radial muscle Ciliary muscle Gastrointestinal function Bronchodilation [beta-2] Contraction [alpha-1] Relaxation [beta-2] Decreased motility [alpha-1,-2 beta-1, -2] Bronchoconstriction [muse] Relaxation [muse] Contraction [muse] Increased motility and secretion [muse]... 

Greenwood-Van Meerveld B, Gardner CJ, Little PJ, et al. Preclinical studies of opioids and opioid antagonists on gastrointestinal function. Neurogastroenterol Motil. 2004 16(suppl 2) 46-53. 

For almost one century, acetylcholine has been recognized as a neurotransmitter both in the central nervous system and the peripheral nervous system. In the peripheral nervous system, acetylcholine has been identified as the neurotransmitter of autonomic ganglia and the neuromuscular junction. Acetylcholine is involved in different peripheral functions such as heart rate, blood flow, gastrointestinal tract motility, and sweat production and smooth muscle activity. In the CNS, cholinergic neurotransmission plays a crucial role in a variety of CNS functions including sensory perception, motor function, cognitive processing, memory, arousal, attention, sleep, nociception, motivation, reward, mood, and psychosis. 

These drugs are muscarinic agonists, used to stimulate gastrointestinal (GI) motility and bladder function. 

B. Octreotide also suppresses pancreatic function, gastric acid secretion, and biliary and gastrointestinal tract motility. 

Numerous in vitro and in vivo techniques have been employed for the study of cannahinoid agonists and antagonists on gastrointestinal functions. These include in vitro studies on isolated gastrointestinal muscle preparations, in vitro peristalsis studies, in vivo gastrointestinal motility studies, in vitro and in vivo... 

Models to identify drug effects on gastrointestinal function should cover gastrointestinal motility, nausea and emesis liability, secretory function (e.g., acidic, ions, hormones), and absorption aspects. Both in vitro and in vivo assessments are available and can be used either in stand-alone SP studies or as specific endpoints integrated into toxicology studies. In addition, novel in sUico tools could also be considered. The choice of approach reflects the focus of a project and may involve isolated cells, organ tissues, and/or whole animals. 

A high concentration of DOPs is found in the olfactory bulb, the neocortex, caudate putamen, and in the spinal cord, but they are also present in the gastrointestinal tract and other peripheral tissues. The functional roles of DOP are less clearly established than for MOP they may have a role in analgesia, gastrointestinal motility, mood and behaviour as well as in cardiovascular regulation [2]. 

Status of the subject s gastrointestinal motility and function (e.g., ability to swallow). 

Mattson, J.L., Spencer, RJ. and Albee, R.R. (1996). A performance standard for clinical and functional observational battery examination of rats. J. Am. Coll. Toxicol. 15 239. Megens, A. A.H.P., Awouters, EH.L. and Niemegeers, C.J.E. (1991). General pharmacology of the four gastrointestinal motility stimulants bethanechol, metoclopramide, trimehutine, and cisapride. Arzneim.-Forsch./Drug Res. 41(f)(6) 631-634. 

Dopamine is an intermediate product in the biosynthesis of noradrenaline. Furthermore it is an active transmitter by itself in basal ganglia (caudate nucleus), the nucleus accumbens, the olfactory tubercle, the central nucleus of the amygdala, the median eminence and some areas in the frontal cortex. It is functionally important, for example in the extra-pyramidal system and the central regulation of emesis. In the periphery specific dopamine receptors (Di-receptors) can be found in the upper gastrointestinal tract, in which a reduction of motility is mediated, and on vascular smooth muscle cells of splanchnic and renal arteries. Beside its effect on specific D-receptors, dopamine activates, at higher concentrations, a- and -adrenoceptors as well. Since its clinical profile is different from adrenaline and noradrenaline there are particular indications for dopamine, like situations of circulatory shock with a reduced kidney perfusion. Dopamine can dose-dependently induce nausea, vomiting, tachyarrhythmia and peripheral vasoconstriction. Dopamine can worsen cardiac ischaemia. 

Spiller R Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders Alterations in 5-HT signaling and metabolism in human disease. Neurogastroenterol Motil 2007 19(Suppl 2) 25. 

If an organ is innervated by both the sympathetic and parasympathetic divisions, a physiologic antagonism typically exists between these divisions. That is, if both divisions innervate the tissue, one division usually increases function, whereas the other decreases activity. For instance, the sympathetics increase heart rate and stimulate cardiac output, whereas the parasympathetics cause bradycardia. However, it is incorrect to state that the sympathetics are always excitatory in nature and that the parasympathetics are always inhibitory. In tissues such as the gastrointestinal tract, the parasympathetics tend to increase intestinal motility and secretion, whereas the sympathetics slow down intestinal motility. The effect of each division on any tissue must be considered according to the particular organ or gland. 

Pathophysiologically, constipation generally results from disordered colonic transit or anorectal function as a result of a primary motility disturbance, certain drugs, or in association with a large number of systemic diseases that affect the gastrointestinal tract. Constipation from any cause may be exacerbated by chronic illnesses that lead to physical or mental impairment and result in inactivity or physical immobility. Additional contributing factors may include a lack of fiber in the diet, generalized muscle weakness, and possibly stress and anxiety. 

Figure 6.4 Types of intestinal motility patterns. Segmentation, tonic contraction, and peristalsis are the three major types of motility patterns observed in the gut. Each serves a specific function for digestion and processing of luminal contents. From E.B. Chang, M.D.Sitrin and D.D.Black (1996) Gastrointestinal motility and neurophysiology. Gastrointestinal, Hepatobiliary, and Nutritional Physiology, Lippincott-Raven, Philadelphia, pp. 27-51...

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