Epinephrine second messenger systems

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

Thyroxine and catecholamine are examples of hormones that are derived from amino acids they are water soluble and circulate in plasma either bound to proteins (thyroxine) or free (catecholamines). Thyroxine binds avidly to three binding proteins and has a half-life of about 7 to 10 days, and the free and unbound catecholamines such as epinephrine have a very short half-life of a minute or less. As do the water-soluble peptide and protein hormones, these hormones interact with membrane-associated receptors and use a second messenger system. 

Norepinephrine (NE) and epinephrine (EPI) act as neurotransmitters and hormones in both the peripheral and central nervous systems (CNS). NE is released from neurons throughout the CNS and periphery to participate in a variety of physiological fimctions, while both NE and EPI are released from the adrenal medulla in response to stress. NE and EPI modulate fluid homeostasis, cardiac fimction, energy metabolism, and may play a role in depression. At the cellular level, these actions are mediated by multiple adrenergic receptor (AR) subtypes and second messenger systems. 

Epinephrine and norepinephrine are catecholamines which, when released from presynaptic nerve endings, function as neurotransmitters (see here). When released from adrenal medulla in response to low blood glucose levels, epinephrine interacts with second-messenger systems in many tissues, with varied effects. In muscle, epinephrine activates adenylate cyclase, with concomitant activation of glycogenolysis and inhibition of glycogen synthesis. 

Receptor proteins (serpentine receptors) that indirectly activate (through GTP-binding proteins, or G proteins) enzymes that generate intracellular second messengers. This is illustrated by the /3-adrenergic receptor system that detects epinephrine (adrenaline) (Section 12.4). 

Research increasingly shows that the distinction between the nervous and endocrine systems is not as clear as was once thought. For example, certain nerve cells, referred to as neurosecretory cells, synthesize and release hormones into the blood. Oxytocin and vasopressin (see p. 125) are two prominent examples. In addition, several neurotransmitters act through second messengers. Epinephrine, which can function as a neurotransmitter and a hormone, induces Tissue-specific effects dependent upon the nature of the receptor to which it binds. 

G-protein receptor systems are widespread in living systems. They are found in many animals and microbes. Both vision and smell in humans depend on G-proteins (Campbell et al., 1999), and glucagon receptors use the system to produce a second messenger called cyclic AMP (cAMP). Receptors for epinephrine, angiotensin, endorphins, and acetylcholine also use this G-protein second messenger mechanism (Sleight and Lieberman, 1995). 

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