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  1. 1. Aut acoids Autacoids are biological factors which act like local hormones, have a brief duration, act near the site of synthesis, and are not blood borne. Autacoids are primarily characterized by the effect they have upon smooth muscle. With respect to vascular smooth muscle, there are both vasoconstrictor and vasodilator autacoids. Vasodilator autacoids can be released during periods of exercise. Their main effect is seen in the skin, allowing for heat loss. The word autacoids comes from the Greek "Autos" (self) and "Acos" (drug). These are local hormones, therefore have a paracrine effect. Some notable autacoids are: eicosanoids, angiotensin, neurotensin, NO (nitric oxide), kinins, histamine, serotonin, endothelins, etc. Se rotonin Serotonin (pronounced /ˌsɛrə ˈtoʊnən/) is a monoamine neurotransmitter that is primarily found in the gastrointestinal (GI) tract and central nervous system (CNS) of animals. Approximately 80 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements. The remainder is synthesized in serotonergic neurons
  2. 2. in the CNS where it has various functions, including the regulation of mood, appetite, sleep, muscle contraction, and some cognitive functions including memory and learning; and in blood platelets where it helps to regulate hemostasis and blood clotting. serotonin stored in platelets is active wherever platelets bind, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic, to aid healing. Hi stamine Most histamine in the body is generated in granules in mast cells or in white blood cells called basophils. Mast cells are especially numerous at sites of potential injury - the nose, mouth, and feet, internal body surfaces, and blood vessels. Non-mast cell histamine is found in several tissues, including the brain, where it functions as a neurotransmitter. Another important site of histamine storage and release is the enterochromaffin-like (ECL) cell of the stomach. mechanism of action Histamine exerts its actions by combining with specific cellular histamine receptors. The four histamine receptors that have been discovered are designated H1 through Type Location Function H1 Found on Causes vasodilation,
  3. 3. bronchoconstriction, bronchial smooth muscle contraction, separation of smooth endothelial cells muscle, (responsible for histamine endothelium, hives), and pain and receptor and central itching due to insect nervous stings; the primary system tissue receptors involved in allergic rhinitis symptoms and motion sickness. H2 Located on Primarily stimulate histamine parietal cells gastric acid secretion receptor Found on central Decreased nervous neurotransmitter H3 system and to release: histamine, histamine a lesser acetylcholine, receptor extent norepinephrine, peripheral serotonin nervous system tissue Found primarily in the basophils and in the bone H4 marrow. It is Plays a role in histamine also found on chemotaxis. receptor thymus, small intestine, spleen, and colon. A ngiotensin
  4. 4. Angiotensin, a protein, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin- angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex. Aldosterone promotes sodium retention in the distal nephron, in the kidney, which also drives blood pressure up. Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system. Neurotensin was first isolated from extracts of bovine hypothalamus based on its ability to cause a visible vasodilation in the exposed cutaneous regions of anesthetized rats. E ndothelins Endothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure (hypertension) and heart disease. Endothelins are 21-amino acid vasoconstricting peptides produced primarily in the endothelium having a key role in vascular homeostasis. Among the strongest vasoconstrictors known, endothelins are implicated in vascular diseases of several organ systems, including the heart, general circulation and brain.[1
  5. 5. There are three isoforms (identified as ET-1, -2, -3) with varying regions of expression and two key receptor types, ETA and ETB. • ETA receptors are found in the smooth muscle tissue of blood vessels, and binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure.[3] • ETB is primarily located on the endothelial cells that line the interior of the blood vessels. When endothelin binds to ETB receptors, this leads to the release of nitric oxide (also called "NO" or endothelium-derived relaxing factor), natriuresis and diuresis (the production and elimination of urine) and mechanisms that lower blood pressure. • Both types of ET receptor are found in the nervous system where they may mediate neurotransmission and vascular functions.[4] • Eico csanoid Pathways in biosynthesis of eicosanoids from arachidonic acid: there are parallel paths from EPA & DGLA. In biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, (EFAs). They exert
  6. 6. complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. The networks of controls that depend upon eicosanoids are among the most complex in the human body. Eicosanoids derive from either omega-3 (ω-3) or omega-6 (ω-6) EFAs. The ω-6 eicosanoids are generally pro-inflammatory; ω-3's are much less so. The amounts and balance of these fats in a person's diet will affect the body's eicosanoid-controlled functions, with effects on cardiovascular disease, triglycerides, blood pressure, and arthritis. Anti- inflammatory drugs such as aspirin and other NSAIDs act by downregulating eicosanoid synthesis. Function and pharmacology Metabolic actions of selected prostanoids and leukotrienes†[15] Stimulation of platelet PGD2 Promotion of sleep TXA2 aggregation; vasoconstriction Smooth muscle contraction; Adipocyte PGE2 inducing pain, heat, 15d-PGJ2 differentiation fever; bronchoconstriction Leukocyte PGF2α Uterine contraction LTB4 chemotaxis PGI2 Inhibition of platelet Cysteinyl- Anaphylaxis;
  7. 7. aggregation; bronchial vasodilation; smooth LTs embryo muscle implantation contraction. † Shown eicosanoids are AA-derived; EPA-derived generally have weaker activity . Role in inflammation Since antiquity, the cardinal signs of inflammation have been known as: calor (warmth), dolor (pain), tumor (swelling) and rubor (redness). The eicosanoids are involved with each of these signs. Redness—An insect's sting will trigger the classic inflammatory response. Short acting vasoconstrictors — TXA2—are released quickly after the injury. The site may momentarily turn pale. Then TXA2 mediates the release of the vasodilators PGE2 and LTB4. The blood vessels engorge and the injury reddens. Swelling—LTB4 makes the blood vessels more permeable. Plasma leaks out into the connective tissues, and they swell. The process also looses pro-inflammatory cytokines. Pain—The cytokines increase COX-2 activity. This elevates levels of PGE2, sensitizing pain neurons. Heat—PGE2 is also a potent pyretic agent. Aspirin and NSAIDS—drugs that block the COX pathways and stop prostanoid synthesis—limit fever or the heat of localized inflammation.
  8. 8. Action of prostanoids Prostanoids mediate local symptoms of inflammation: vasoconstriction or vasodilation, coagulation, pain and fever. Inhibition of cyclooxygenase, specifically the inducible COX-2 isoform, is the hallmark of NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin. COX-2 is responsible for pain and inflammation, while COX-1 is responsible for platelet clotting actions. Prostanoids activate the PPARγ members of the steroid/thyroid family of nuclear hormone receptors, directly influencing gene transcription.[21] Action of leukotrienes Leukotrienes play an important role in inflammation. There is a neuroendocrine role for LTC4 in luteinizing hormone secretion.[22] LTB4 causes adhesion and chemotaxis of leukocytes and stimulates aggregation, enzyme release, and generation of superoxide in neutrophils.[23] Blocking leukotriene receptors can play a role in the management of inflammatory diseases such as asthma (by the drugs montelukast and zafirlukast), psoriasis, and rheumatoid arthritis. The slow reacting substance of anaphylaxis comprises the cysteinyl leukotrienes. These have a clear role in pathophysiological conditions such as asthma, allergic rhinitis and other nasal allergies, and have been implicated in atherosclerosis and inflammatory gastrointestinal diseases.[24] They are potent bronchoconstrictors, increase vascular permeability in
  9. 9. postcapillary venules, and stimulate mucus secretion. They are released from the lung tissue of asthmatic subjects exposed to specific allergens and play a pathophysiological role in immediate hypersensitivity reactions Along with PGD, they function in effector cell trafficking, antigen Enteric nervous system The enteric nervous system (ENS) is a subdivision of the Peripheral Nervous System, that directly controls the gastrointestinal system.drived from neuralcrest Function The ENS is capable of autonomous functionssuch as the coordination of reflexes, although it receives considerable innervation from the
  10. 10. autonomic nervous system and thus is often considered a part of the ANS. Its study is the focus of neurogastroenterology. The ENS can be damaged by ischemia. Transplantation has been described as a theoretical possibility. Anatomy The ENS consists of some one hundred million neurons one thousandth of the number of neurons in the brain, and considerably more than the number of neurons in the spinal cord. The enteric nervous system is embedded in the lining of the gastrointestinal system. The neurons of the ENS are collected into two types of ganglia: myenteric (Auerbach's) and submucosal (Meissner's) plexuses Myenteric plexuses are located between the inner and outer layers of the muscularis externa, while submucosal plexuses are located in the submucosa. Complexity The enteric nervous system has been described as a "second brain" There are several reasons for this. The enteric nervous system can operate autonomously. It normally communicates with the CNS through the parasympathetic (eg, via the vagus nerve) and sympathetic (eg, via the prevertebral ganglia) nervous systems. However, vertebrate studies show that when the vagus nerve is severed, the enteric nervous system continues to function. In vertebrates the enteric nervous system includes efferent neurons, afferent neurons, and interneurons, all of which make the enteric nervous system capable of carrying
  11. 11. reflexes and acting as an integrating center in the absence of CNS input. The sensory neurons report on mechanical and chemical conditions. Through intestinal muscles, the motor neurons control peristalsis and churning of intestinal contents. Other neurons control the secretion of enzymes. The enteric nervous system also makes use of more than 30 neurotransmitters, most of which are identical to the ones found in CNS, such as acetylcholine, dopamine, and serotonin. The enteric nervous system has the capacity to alter its response depending on such factors as bulk and nutrient composition. In addition, ENS contains support cells which are similar to astroglia of the brain and a diffusion barrier around the capillaries surrounding ganglia which is similar to the blood-brain barrier of cerebral blood vessels.[10] The myenteric The plexus of the plexus from the submucosa from rabbit. X 50. the rabbit. X 50.
  12. 12. [hide] v•d•e Digestive system, physiology: gastrointestinal phy Chief cells (Peps Parietal cells (Ga Exocrine Intrinsic factor) · Upper GI (Mucus) ProcessesSwallowing · Vo FluidsSaliva · Gastric ju M Enteric nervous systemple Au G D (so EC (H en Endocrine/paracrinece GI tract ce ce Lower GI En ce En ce Br BorderPa En FluidsIn Se co M Processes co Bo De Either/both Peristalsis (Inters