Second Messenger Systems

Hormones and neurotransmitters can be thought of as signals and their receptors as signal detectors. Receptors respond to a bound ligand by initiating a series of reactions that ultimately result in specific intracellular responses. Second messenger molecules, so named because they intervene between the original extracellular messenger (the neurotransmitter or hormone) and the ultimate intracellular effect, are part of the cascade of events that converts (transduces) ligand binding into a response. Two of the most widely recognized second messenger systems are the calcium/phosphatidylinositol system  and the adenylyl cyclase (adenylate cyclase) system, which is particularly important in regulating the pathways of intermediary metabolism. Both involve the binding of ligands, such as epinephrine or glucagon, to specific G protein–coupled receptors (GPCR) on the cell (plasma) membrane. GPCR are characterized by an extracellular ligand-binding domain, seven transmembrane α helices, and an intracellular domain that interacts with trimeric G proteins (Fig. 1). [Note: Insulin, another key regulator of metabolism, binds a membrane tyrosine kinase receptor  and not a GPCR.]

Figure 1:  Structure of a typical G protein–coupled receptor of the plasma membrane.