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Pharmacological studies using synaptosomes have also provided evidence that the amount of transmitter that is released following their depolarisation is regulated by the activation of presynaptic receptors purchase 100 mg kamagra effervescent visa. After washing the synaptosomes buy 100 mg kamagra effervescent amex, the release of 3H into the perfusate is then measured using (extremely sensitive)liquid scintillation counting buy 100 mg kamagra effervescent otc. Another unjustified assumption is that the radiolabelled transmitter mixes freely with the endogenous (unlabelled)store buy kamagra effervescent 100 mg with visa. Finally order kamagra effervescent 100 mg free shipping, as it is the radiolabel, rather than the actual transmitter itself, which is being measured it must be established that the label remains attached to the neurotransmitter. For instance, [3H]glutamate can be turned into [3H]GABA or [3H]glutamine and so care must be taken to ensure that any findings with 3H refer to release of [3H]glutamate rather than that of its metabolites. The main advantage of using slices is that, either by crudely passing currents across them or, in some cases, stimulating a NEUROTRANSMITTER RELEASE 85 Figure 4. On the assumption that, although concentrated in nerve terminals, the neurotransmitter will also be found in cell bodies and axons, it is likely that A will be almost entirely in synaptosomes, C mostly in the cytoplasm, while B will be more evenly divided. Brain tissue is homogenised and spun at 10006g for 10 min to remove cell debris. The supernatant (S1) is spun at 20 0006g for 10 min and the pellet (P2), containing synaptosomes and mitochondria, is spun through two layers of sucrose for 2 h at 50 0006g. Thus, synaptosomes separate from other elements of the 20 0006g pellet and settle at the interface between 0. Because the three-dimensional integrity of the tissue is maintained, they can also be used to study modulation of transmitter release by heteroceptors (see below). One approach, and the first to be adopted, is to study transmitter release from slices which have been preloaded with radiolabelled transmitter. This involves comparing the effects of a test drug on the amount of transmitter released in response to a reference pulse and a second identical test pulse. As with 86 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION synaptosomes, however, it cannot be assumed that incubation of slices in a medium containing radiolabelled transmitter results in its even distribution throughout the slice. Also, the problem of continuous dilution of the radiolabelled store with newly synthesised (unlabelled)transmitter must be borne in mind. Modern sensitive chromatographic and voltammetric techniques now make it possible to estimate the release of unlabelled endogenous transmitter from slices of brain tissue (commonly the hippocampus and striatum)or spinal cord (Fig. However, whatever analytical method is used, the thickness of the slice is paramount. It is important to maintain the balance between preserving the integrity of the tissue (the thicker the slice, the better)against maintaining tissue viability by perfusion with oxygenated aCSF (the thinner the slice, the better). TECHNIQUES IN VIVO The cortical cup The cortical cup has been used for many years to monitor changes in transmitter release induced by physiological and pharmacological stimuli (Fig. In the past, it was used most commonly to study release of amino acids and acetylcholine. Measurements by HPLC and fluorescence detection after reaction of amino acids with o-phthalaldehyde: 1, aspartate; 2, glutamate; 3, asparagine; 4, serine; 5, glutamine; 6, histidine; 7, homoserine (internal standard); 8, glycine; 9, threonine; 10, arginine; 11, taurine; 12, alanine; 13, GABA; 14, tyrosine. Glutamate concentration is almost 1 pmol/ml which represents a release rate of 30 pmol/min/mg tissue NEUROTRANSMITTER RELEASE 87 Figure 4. For the rat, the overall diameter is 6±7 mm and a typical flow rate is 50 ml/min been adopted in studies of peptide and purine release as well (e. Transmitters released from neurons near the surface of the brain accumulate in the cup and their concentration in the aCSF can be used as a crude index of release rate. The importance of this technique is that it enabled, for the first time, the monitoring of transmitter release in freely moving animals. Microdialysis This is a modification of the earlier push±pull cannula which could be used in anaesthetised animals only. The microdialysis probe which has an outside diameter of about 250 mm (Fig. Solutes (including neurotransmitters)in the extracellular fluid of the brain diffuse down their concentration gradient into the probe. By taking samples of the effluent dialysate at regular intervals it is possible to monitor changes in transmitter release.

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CHAPTER 33 The Thyroid Gland 603 Thyroid Hormones Are Essential for involved; the amounts of oxygen consumed and body heat Normal Body Growth produced depend on total body activity generic kamagra effervescent 100 mg with visa. The thyroid hormones are important factors regulating the Thermogenic Action of the Thyroid Hormones buy kamagra effervescent 100mg mastercard. For example cheap kamagra effervescent 100mg on line, an individual who hormones regulate the basal rate at which oxidative phos- is deficient in thyroid hormones buy kamagra effervescent 100 mg line, who does not receive thy- phorylation takes place in cells kamagra effervescent 100 mg mastercard. As a result, they set the roid hormone therapy during childhood, will not grow to a basal rate of body heat production and of oxygen con- normal adult height. A major way Thyroid hormone levels in the blood must be within thyroid hormones promote normal body growth is by normal limits for basal metabolism to proceed at the rate stimulating the expression of the gene for growth hor- needed for a balanced energy economy of the body. For ex- mone (GH) in the somatotrophs of the anterior pituitary ample, if thyroid hormones are present in excess, oxidative gland. In a thyroid hormone-deficient individual, GH phosphorylation is accelerated, and body heat production synthesis by the somatotrophs is greatly reduced and con- and oxygen consumption are abnormally high. The con- sequently GH secretion is impaired; therefore, a thyroid verse occurs when the blood concentrations of T4 and T3 hormone-deficient individual will also be GH-deficient. The fact that thyroid hormones af- this condition occurs in a child, it will cause growth retar- fect the amount of oxygen consumed by the body has been dation, largely a result of the lack of the growth-promot- used clinically to assess the status of thyroid function. This measurement is the thyroid hormones have additional effects on growth. Not all tissues are sensitive to the thermo- stimulate the synthesis of structural proteins of mitochon- genic action of thyroid hormones. Tissues and organs that dria, as well as the formation of many enzymes involved in give this response include skeletal muscle, the heart, the intermediary metabolism and oxidative phosphorylation. These are also tissues in which thy- Thyroid hormones also promote the calcification and, roid hormone receptors are abundant. The adult brain, hence, the closure, of the cartilaginous growth plates of the skin, lymphoid organs, and gonads show little thermogenic bones of the skeleton. How the thyroid hormones promote calcification adult brain, these tissues contain few thyroid hormone re- of the growth plates of bones is not understood. The thermo- Energy Economy of the Body genic action of the thyroid hormones is poorly under- stood at the molecular level. The thermogenic effect When the body is at rest, about half of the ATP produced takes many hours to appear after the administration of by its cells is used to drive energy-requiring membrane thyroid hormones to a human or animal, probably be- transport processes. The remainder is used in involuntary cause of the time required for changes in the expression muscular activity, such as respiratory movements, peri- of genes involved. T3 is known to stimulate the synthesis stalsis, contraction of the heart, and in many metabolic of cytochromes, cytochrome oxidase, and Na /K -AT- reactions requiring ATP, such as protein synthesis. This action suggests that T3 may energy required to do this work is eventually released as regulate the number of respiratory units in these cells, af- body heat. A greater rate of oxidative phosphorylation would Basal Oxygen Consumption and Body Heat Production. The major site of ATP production is the mitochondria, Thyroid hormone also stimulates the synthesis of uncou- where the oxidative phosphorylation of ADP to ATP takes pling protein-1 (UCP-1) in brown adipose tissue. The rate of oxidative phosphorylation depends on synthesized by ATP synthase in the mitochondria when pro- the supply of ADP for electron transport. UCP-1 acts is, in turn, a function of the amount of ATP used to do work. As the protons move ATP is used and more ADP is generated, increasing the rate down their electrochemical gradient uncoupled from ATP syn- of oxidative phosphorylation. Adult humans have little phosphorylation occurs is reflected in the amount of oxygen brown adipose tissue, so it is not likely that UCP-1 makes a consumed by the body because oxygen is the final electron significant contribution to nutrient oxidation or body heat acceptor at the end of the electron transport chain. However, several uncoupling proteins (UCP-2 Activities that occur when the body is not at rest, such and UCP-3) have recently been discovered in many tissues, as voluntary movements, use additional ATP for the work and their expression is regulated by thyroid hormones. Thyroid Hormones Development of CNS Inhibit nerve cell replication Thyroid Hormones Stimulate Intermediary Stimulate growth of nerve cell bodies Metabolism Stimulate branching of dendrites Stimulate rate of axon myelinization In addition to their ability to regulate the rate of basal en- Body growth Stimulate expression of gene for ergy metabolism, thyroid hormones influence the rate at GH in somatotrophs which most of the pathways of intermediary metabolism Stimulate synthesis of many operate in their target cells. When thyroid hormones are structural and enzymatic proteins deficient, pathways of carbohydrate, lipid, and protein me- Promote calcification of growth plates of bones tabolism are slowed, and their responsiveness to other reg- Basal energy economy of Regulate basal rates of oxidative ulatory factors, such as other hormones, is decreased. How- the body phosphorylation, body heat ever, these same metabolic pathways run at an abnormally production, and oxygen high rate when thyroid hormones are present in excess. The amplifying effect of thy- pathways of carbohydrate, lipid, roid hormones on intermediary metabolism is mediated and protein metabolism through the activation of genes encoding enzymes in- Thyroid-stimulating Inhibit TSH secretion by decreasing volved in these metabolic pathways.

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Because humans stand and walk on Placental attachment for young (within two appendages generic 100 mg kamagra effervescent mastercard, our style of locomotion is said to be uterus) bipedal order 100mg kamagra effervescent otc. Upright posture imposes other diagnostic structural features kamagra effervescent 100 mg line, such as the sigmoid (S-shaped) curvature of the FIGURE 2 generic kamagra effervescent 100mg. Body Organization and © The McGraw−Hill Anatomy order kamagra effervescent 100mg with mastercard, Sixth Edition Organization, and the Anatomical Nomenclature Companies, 2001 Human Organism 26 Unit 2 Terminology, Organization, and the Human Organism Creek Tarsier Aye-aye Gorilla Human FIGURE 2. Cerebrum Optic lobe Cerebellum Cerebrum Codfish Frog Chimpanzee Cerebellum Alligator Goose Human Creek Horse FIGURE 2. Body Organization and © The McGraw−Hill Anatomy, Sixth Edition Organization, and the Anatomical Nomenclature Companies, 2001 Human Organism Chapter 2 Body Organization and Anatomical Nomenclature 27 (a) (b) (c) (d) (e) (f) FIGURE 2. The human thumb is structurally Taxon Grouping Characteristics adapted for tremendous versatility in grasping objects. Kingdom Animalia Eucaryotic cells without walls, plastids, The saddle joint at the base of the thumb allows a wide or photosynthetic pigments range of movement (see fig. All primates have op- Phylum Chordata Dorsal hollow nerve cord; notochord; posable thumbs. Humans, like no other Subphylum Vertebrata Vertebral column animals, have developed articulated speech. The anatomi- Class Mammalia Mammary glands; hair; convoluted cal structure of our vocal organs (larynx, tongue, and lips), cerebrum; heterodont dentition and our well-developed brain have made this possible. Order Primates Well-developed brain; prehensile hands Family Hominidae Large cerebrum, bipedal locomotion 5. Although this characteristic is well de- veloped in several other animals, it is also keen in humans. Genus Homo Flattened face; prominent chin and nose with inferiorly positioned nostrils Our eyes are directed forward so that when we focus on an Species sapiens Largest cerebrum object, we view it from two angles. Stereoscopic vision gives us depth perception, or a three-dimensional image. Body Organization and © The McGraw−Hill Anatomy, Sixth Edition Organization, and the Anatomical Nomenclature Companies, 2001 Human Organism 28 Unit 2 Terminology, Organization, and the Human Organism We also differ from other animals in the number and The human body contains many distinct kinds of cells, arrangement of our vertebrae (vertebral formula), the kinds and each specialized to perform specific functions. Examples of spe- number of our teeth (tooth formula), the degree of development cialized cells are bone cells, muscle cells, fat cells, blood cells, of our facial muscles, and the structural organization of various liver cells, and nerve cells. The human characteristics just described account for the splendor of our cultural achievements. As bipedal animals, we have our hands free to grasp and manipulate objects with our op- Tissue Level posable thumbs. We can store information in our highly developed brain, make use of it at a later time, and even share our learning Tissues are layers or groups of similar cells that perform a com- through oral or written communication. The entire body is composed of only four princi- pal kinds of tissues: epithelial, connective, muscular, and nervous Knowledge Check tissue. An example of a tissue is the muscle within the heart, whose function it is to pump the blood through the body. Why are humans considered members outer layer of skin (epidermis) is a tissue because it is composed of the phylum Chordata? Organ Level An organ is an aggregate of two or more tissue types that per- BODY ORGANIZATION forms a specific function. Examples of organs are the Structural and functional levels of organization characterize the heart, spleen, pancreas, ovary, skin, and even any of the bones human body, and each of its parts contributes to the total organism. Each organ usually has one or more primary tis- Objective 4 Identify the components of a cell, tissue, organ, sues and several secondary tissues. In the stomach, for example, and system, and explain how these structures relate to one the inside epithelial lining is considered the primary tissue be- another in constituting an organism. Secondary tissues of the stomach are the con- Objective 5 Describe the general function of each system. Cellular Level The cell is the basic structural and functional component of System Level life. Humans are multicellular organisms composed of 60 to The systems of the body constitute the next level of structural 100 trillion cells. A body system consists of various organs that have such vital functions of life as metabolism, growth, irritability similar or related functions. Examples of systems are the circula- (responsiveness to stimuli), repair, and replication are car- tory system, nervous system, digestive system, and endocrine sys- ried on.

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