Most cells of the body have receptors for catecholamines and, thus, are their target cells. There are four structurally related forms of catecholamine receptors, all of which are transmembrane proteins: aw a2, Pi, and P2. All can bind epinephrine or NE, to varying extents (see Chapter 3).
Fight-or-Flight Response. Epinephrine and NE produce widespread effects on the cardiovascular system, muscular system, and carbohydrate and lipid metabolism in liver, muscle, and adipose tissues. In response to a sudden rise in catecholamines in the blood, the heart rate accelerates, coronary blood vessels dilate, and blood flow to the skeletal muscles is increased as a result of vasodilation (but vasoconstriction occurs in the skin). Smooth muscles in the airways of the lungs, gastrointestinal tract, and urinary bladder relax. Muscles in the hair follicles contract, causing piloerection. Blood glucose level also rises. This overall reaction to the sudden release of catecholamines is known as the fight-or-flight response (see Chapter 6).
Catecholamines and the Metabolic Response to Hypoglycemia. Catecholamines secreted by the adrenal medulla and NE released from sympathetic postganglionic nerve terminals are key agents in the body's defense against hypoglycemia. Catecholamine release usually starts when the blood glucose concentration falls to the low end of the physiological range (60 to 70 mg/dL). A further decline in blood glucose concentration into the hy-poglycemic range produces marked catecholamine release. Hypoglycemia can result from a variety of situations, such as insulin overdosing, catecholamine antagonists, or drugs that block fatty acid oxidation. Hypoglycemia is always a dangerous condition because the CNS will die of ATP deprivation in extended cases. The length of time pro found hypoglycemia can be tolerated depends on its severity and the individual's sensitivity.
When the blood glucose concentration drops toward the hypoglycemic range, CNS receptors monitoring blood glucose are activated, stimulating the neural pathway leading to the fibers innervating the chromaffin cells. As a result, the adrenal medulla discharges catecholamines. Sympathetic postganglionic nerve terminals also release norepinephrine.
Catecholamines act on the liver to stimulate glucose production. They activate glycogen phosphorylase, resulting in the hydrolysis of stored glycogen, and stimulate glu-coneogenesis from lactate and amino acids. Cate-cholamines also activate glycogen phosphorylase in skeletal muscle and adipose cells by interacting with P receptors, activating adenylyl cyclase and increasing cAMP in the cells. The elevated cAMP activates glycogen phos-phorylase. The glucose 6-phosphate generated in these cells is metabolized, although glucose is not released into the blood, since the cells lack glucose-6-phosphatase. The glucose 6-phosphate in muscle is converted by glycolysis to lactate, much of which is released into the blood. The lactate taken up by the liver is converted to glucose via glu-coneogenesis and returned to the blood.
In adipose cells, the rise in cAMP produced by catecholamines activates hormone-sensitive lipase, causing the hydrolysis of triglycerides and the release of fatty acids and glycerol into the bloodstream. These fatty acids provide an alternative substrate for energy metabolism in other tissues, primarily skeletal muscle, and block the phosphorylation and metabolism of glucose.
During profound hypoglycemia, the rapid rise in blood catecholamine levels triggers some of the same metabolic adjustments that occur more slowly during fasting. During fasting, these adjustments are triggered mainly in response to the gradual rise in the ratio of glucagon to insulin in the blood. The ratio also rises during profound hypoglycemia, reinforcing the actions of the catecholamines on glycogenolysis, gluconeogenesis, and lipolysis. The catecholamines released during hypoglycemia are thought to be partly responsible for the rise in the glucagon-to-insulin ratio by directly influencing the secretion of these hormones by the pancreas. Catecholamines stimulate the secretion of glucagon by the alpha cells and inhibit the secretion of insulin by beta cells (see Chapter 35). These catecholamine-mediated responses to hypoglycemia are summarized in Table 34.4.
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