Second messengers hormonal secretion

Fig. 11.10. Heptahelical Receptors and Second Messengers. The secreted chemical messenger (hormone, cytokine, or neurotransmitter) is the first messenger, which binds to a plasma membrane receptor such as the heptahelical receptors. The activated hormone-receptor complex activates a heterotrimeric G protein and via stimulation of membrane-bound enzymes, different G-proteins lead to generation of one or more intracellular second messengers, such as cAMP, diacylglycerol (DAG), or inositol trisphosphate (IP3).

Several groups have shown that hormonal stimuli which lead to NaCl secretion in normal tissues fail to do so in CF tissues (reviewed in [17,18,60]). The production of the second messenger cAMP was unimpeded in these CF tissues. Hence it was... 

Anti-diuretic hormone is a small peptide shown as Figure 8.9, which is secreted by the pituitary gland located at the base of the brain. The cellular actions of ADH are mediated by activation of a G-protein linked receptor generating cAMP as second messenger. Absence of ADH or a functional defect in the action of ADH-stimulated water reabsorption in the collecting duct results in the condition diabetes insipidus, characterized by the passing of large volumes (= diabetes) of dilute (= insipidus) urine. 

The biosynthesis of peptide hormones and proteohormones, as well as their secretion, is controlled by higher-order regulatory systems (see p. 372). Calcium ions are among the substances involved in this regulation as second messengers an increase in calcium ions stimulates synthesis and secretion. 

Hormonal gastrin secreted by the G cells of the gastric antrum stimulates the parietal cells directly through gastrin receptors (increased Ca2+ as second messenger), and probably also indirectly by acting on enterochromaffin-iike (ECL) cells to release histamine. 

Catecholamines produced in the brain and in other neural tissues function as neurotransmitters, but epinephrine and norepinephrine are also hormones, synthesized and secreted by the adrenal glands. Like the peptide hormones, catecholamines are highly concentrated within secretory vesicles and released by exocytosis, and they act through surface receptors to generate intracellular second messengers. They mediate a wide variety of physiological responses to acute stress (see Table 23-6). 

The outline of another important second-messenger system was elucidated during the last few years. Chemical messengers that act via this system include a variety of hormones (e.g., catecholamines, vasopressin, and angiotensin) as well as some neurotransmitters (e.g., acetylcholine acting on pancreatic acinar cells to stimulate secretion of digestive... 

The G protein-GTP complexes related to receptors for these hormones activate adenylyl cyclase, which synthesizes the second messenger cAMP. Cyclic AMP activates protein kinases, which phosphorylate certain intracellular proteins (eg, enzymes), thus producing the hormonal effect. Conversely, dopamine binding to lactotroph receptors causes conformational changes in its G protein that reduce the activity of adenylyl cyclase and inhibit the secretion of prolactin. 

A schematic representation of the cellular mechanisms through which agonists, such as dopamine, stimulate PTH release and calcium inhibits hormonal secretion is shown in Figure 11. In this schema, cAMP is a stimulatory second messenger while cytosolic calcium serves to inhibit hormone release by acting at several loci within the cell. The detailed molecular mechanisms through which cAMP and cellular calcium modulate cellular function remain to be determined. 

Phospholipids and glycosphingolipids are amphipathic lipid constituents of membranes (Chapter 10). They play an essential role in the synthesis of plasma lipoproteins (Chapter 20) and eicosanoids (Chapter 18). They function in transduction of messages from cell surface receptors to second messengers that control cellular processes (Chapter 30) and as surfactants. Cholesterol is mainly of animal origin and is an essential constituent of biomembranes (Chapter 10). In plasma, cholesterol is associated with lipoproteins (Chapter 20). Cholesterol is a precursor of bile acids formed in the liver of steroid hormones secreted by adrenals, gonads, and placenta and 7-dehydrocholesterol of vitamin D formed in the skin. In tissues, cholesterol exists primarily in the unesterified form (e.g., brain and erythrocytes), although appreciable quantities are esterified with fatty acids in liver, skin, adrenal cortex, and plasma lipoproteins. 

Intracellular ionized calcium acts as a second messenger, coupling the action of a hormone or electrical impulse (the first messenger) on the outside of the cell to intracellular events, such as hormone or protein secretion, protein kinase activity, or muscle contraction. The effect of Ca on intracellular processes is often mediated by a small calcium-binding protein, such as troponin C in muscle (Chapter 21) or calmodulin in many other cells (Chapters 15 and 30). Synthesis of these calciumbinding proteins is not directly affected by vitamin D or any of its metabolites. Many stimuli that affect permeability to calcium also activate membrane-bound adenylate cyclase and increase the intracellular concentration of cAMP (Chapter 30). 

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