Figure 747

Cyclic adenosine monophosphate (cAMP) mechanism by which many hormones exert their control of cell function. ADP, adenosine diphosphate; ATP, adenosine triphosphate.

the conversion of a small amount of cytoplasmic adenosine triphosphate (ATP) into cAMP inside the cell. This then activates cAMP-dependent protein kinase, which phosphorylates specific proteins in the cell, triggering biochemical reactions that ultimately lead to the cell's response to the hormone.

Once cAMP is formed inside the cell, it usually activates a cascade of enzymes. That is, first one enzyme is activated, which activates a second enzyme, which activates a third, and so forth. The importance of this mechanism is that only a few molecules of activated adenylyl cyclase immediately inside the cell membrane can cause many more molecules of the next enzyme to be activated, which can cause still more molecules of the third enzyme to be activated, and so forth. In this way, even the slightest amount of hormone acting on the cell surface can initiate a powerful cascading activating force for the entire cell.

If binding of the hormone to its receptors is coupled to an inhibitory G protein (denoted Gt protein), adenylyl cyclase will be inhibited, reducing the formation of cAMP and ultimately leading to an inhibitory action in the cell. Thus, depending on the coupling of the hormone receptor to an inhibitory or a stimulatory G protein, a hormone can either increase or decrease the concentration of cAMP and phosphorylation of key proteins inside the cell.

The specific action that occurs in response to increases or decreases of cAMP in each type of target cell depends on the nature of the intracellular machinery—some cells have one set of enzymes, and other cells have other enzymes. Therefore, different functions are elicited in different target cells, such as initiating synthesis of specific intracellular chemicals, causing muscle contraction or relaxation, initiating secretion by the cells, and altering cell permeability.

Thus, a thyroid cell stimulated by cAMP forms the metabolic hormones thyroxine and triiodothyronine, whereas the same cAMP in an adrenocortical cell causes secretion of the adrenocortical steroid hormones. In epithelial cells of the renal tubules, cAMP increases their permeability to water.

The Cell Membrane Phospholipid Second Messenger System

Some hormones activate transmembrane receptors that activate the enzyme phospholipase C attached to the inside projections of the receptors (Table 74-3). This enzyme catalyzes the breakdown of some phos-pholipids in the cell membrane, especially phos-phatidylinositol biphosphate (PIP2), into two different second messenger products: inositol triphosphate (IP3) and diacylglycerol (DAG). The IP3 mobilizes calcium ions from mitochondria and the endoplasmic

Table 74-3

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