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The more important a variable cheap 800mg aciclovir mastercard, the opening or closing of ion channels are mediated via 2 2 the more numerous and complicated are the mechanisms transient changes in cytosolic [Ca ]. Disease or death is often resting cells is low, about 10 M, and far below extracel- 2 2 the result of dysfunction of homeostatic mechanisms. Cytosolic [Ca ] is reg- The effectiveness of homeostatic mechanisms varies ulated by the binding of calcium to intracellular proteins, over a person’s lifetime. Some homeostatic mechanisms are transport is regulated by adenosine triphosphate (ATP)-de- not fully developed at the time of birth. For example, a pendent calcium pumps in mitochondria and other or- newborn infant cannot concentrate urine as well as an adult ganelles (e. For example, older adults are less able to tol- minished ATP production can lead to an abnormally ele- 2 2 erate stresses, such as exercise or changing weather, than vated cytosolic [Ca ]. Intracellular Homeostasis Is Essential for Normal Cell Function Negative Feedback Promotes Stability; Feedforward Control Anticipates Change The term homeostasis has traditionally been applied to the in- ternal environment—the extracellular fluid that bathes our Engineers have long recognized that stable conditions can be tissues—but it can also be applied to conditions within achieved by negative-feedback control systems (Fig. In fact, the ultimate goal of maintaining a constant in- Feedback is a flow of information along a closed loop. The ternal environment is to promote intracellular homeostasis, components of a simple negative-feedback control system and toward this end, conditions in the cytosol are closely include a regulated variable, sensor (or detector), controller regulated. Each component controls the The many biochemical reactions within a cell must be next component. Various disturbances may arise within or tightly regulated to provide metabolic energy and proper rates of synthesis and breakdown of cellular constituents. Metabolic reactions within cells are catalyzed by enzymes and are therefore subject to several factors that regulate or Feedforward Feedforward path controller influence enzyme activity. End-product inhibition is an example of negative-feed- Feedback back control (see below). Cells reg- The regulated variable is sensed, and information about its level is fed back to a feedback controller, which compares it to a desired ulate their pH via mechanisms for buffering intracellular value (set point). If there is a difference, an error signal is gener- hydrogen ions and by extruding H into the extracellular ated, which drives the effector to bring the regulated variable fluid (see Chapter 25).

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Pressure receptors respond to pressure cheap aciclovir 200 mg fast delivery, vibration, and stretch Receptors may also be classified on the basis of sensory and are commonly found in the hypodermis of the skin and in adaptation (accommodation). The tactile and pressure re- burst of activity when a stimulus is first applied, but then quickly ceptors are summarized in table 15. Receptors with this response pattern are Corpuscles of Touch called phasic receptors. Receptors that produce a relatively con- A corpuscle of touch (Meissner’s corpuscle) is an oval receptor stant rate of firing as long as the stimulus is maintained are composed of a mass of dendritic endings from two or three nerve known as tonic receptors. These corpuscles are Phasic receptors alert us to changes in sensory stimuli and are numerous in the hairless portions of the body, such as the eye- in part responsible for the fact that we can cease paying atten- lids, lips, tip of the tongue, fingertips, palms of the hands, soles of tion to constant stimuli. Corpuscles of touch lie and touch, for example, adapt rapidly; bathwater feels hotter when within the papillary layer of the dermis, where they are especially we first enter it. Sensory Organs © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 Chapter 15 Sensory Organs 491 (see chapter 5). Sensations of fine or light touch are perceived as heat receptors and the latter cold receptors. The bulbs of Krause respond to light touches an object to determine its texture. Any mother can attest to the calming effect that holding and Braille symbols consist of dots that are raised 1 mm from the patting have on a crying baby. It has been known that the surface of the page and separated from each other by 2. There enced braille readers can scan words at about the same speed that a is now evidence that touching and caressing newborns actually en- sighted person can read aloud—a rate of about 100 words per minute. Even premature infants grow and mature faster if they Free Nerve Endings are regularly held and touched. Free nerve endings are the least modified and the most superfi- Experiments with rats have shown that licking and grooming by the mother stimulate the secretion of growth hormones in her pups cial of the tactile receptors. The amount of growth hormone is significantly reduced in lower layers of the epidermis, where they end as knobs between isolated pups that are not licked or groomed.

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Salamone generic aciclovir 800 mg otc, Cousins and Snyder (1997) in fact suggest that the function of DA in the nucleus accumbens should not be described by terms such as motivation, reinforcement and reward. Rather it should be considered to mediate the higher-order motor and sensory processes that are important for the activation of aspects of motivation and responsiveness to conditioned stimuli. DOPAMINE RECEPTORS, FUNCTION AND SYNERGISM With the discovery of five distinct DA receptors within two major families, one might hope that the effects of the different DA pathways would be mediated through different receptors. Thus only D2 antagonists have anti-emetic activity and only D2 agonists, like bromocriptine, reduce plasma prolactin levels. In this condition, however, some D1 stimulation may augment the effect of the D2 agonists (Chapter 14), suggesting a synergism between the two receptors. This synergism has been observed in both electophysiological studies on striatal neuron activity and some animal behaviours. The electrophysiological studies of DA function in the striatum, reported above, suggest some similarities between D1- and D2-mediated effects. A clear synergism has been seen in fact, on the so-called type IDA neurons in the ventral tegmentum in vitro (Momiyama, Naoyuki and Saso 1993). The D2 agonist quinpirole produced hyperpolarisation (4K‡ conductance) and reduced-action potential numbers but the D1 agonist SKF 38393 had no effect alone. When given with quinpirole, however, it increased the ability of the D2 agonist to raise the threshold for action potential DOPAMINE 159 Figure 7. The level of behavioural and motor response to dopamine agonists is shown by the extent of shading in the response box. A mixed agonist, including DA itself, can produce a full response (a) by activating both D1 and D2 receptors. A D1 agonist alone (b) has little effect compared with a D2 agonist alone (c). Behaviourally, a D1 agonist like SKF 38593 has few effects alone in rats apart from inducing grooming and some sniffing. By contrast, the D2 agonist bromocriptine produces a marked behavioural stereotypy during which animals move avidly around the cage sniffing, gnawing, digging and then rearing.

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