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Burned in "Fight or Flight" response

FIGURE 11-11 Possible scenario for the mode of action of epinephrine on the hepatocyte to generate glucose from increased glycogenolysis and gluconeogenesis. Epinephrine is released through the stress pathway by way of a two-neuron system, ending on an acetylcholinergic neuron innervating the adrenal medulla. The acetylcholine binds to membrane receptors on the chromaffin cell, causing an increased cellular uptake of Ca2+. This results in the release of epinephrine (and other components) from granules through exocytosis. The epinephrine released binds to a-receptors on hepatocytes (and on cells that bring about contraction and increased blood pressure), causing an elevation in the cytosolic Ca2+ concentration. This may be brought about by activating the arreceptor-linked Ca2+ channel. Elevated Ca2+ stimulates phosphoryl-ase kinase activity, glycogen synthase I (the effect of Ca2+ may be indirect here), and gluconeogenesis, all of which lead to the generation of glucose and an increase in circulating glucose levels for use in fight-or-flight responses in adapting to the original stress.

is an increase in the number of /3-receptors without a detectable change in the number of a-receptors.

Desensitization is another regulatory aspect of adrenergic receptors. Prolonged exposure to an agonist such as epinephrine leads to decreased responsiveness to a given target tissue. This desensitization occurs with both a- and /3-receptors. The mechanisms of these responses are summarized in Figure 11-14. Certain cells in culture contain adenylate cyclase but lack /3-

adrenergic receptors. The membranes have been isolated from such cells and combined with extracts from other cells containing the receptor. The entire system can be reconstituted in the formerly receptor-deficient membrane. The reconstituted system reproduces the properties of a normal cell membrane in terms of the effects of agonists and antagonists in stimulating adenylate cyclase. Such experiments tend to strengthen our conception of the receptor system.

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