Cells in the human body, numbering in the billions, possess unique functions. However, these functions are closely coordinated and regulated through the use of external chemical signals. These chemical signals, which include hormones, neurotransmitters, growth factors, odorants, and byproducts of cellular metabolism, serve as messengers that facilitate communication between cells. In addition to chemical signals, mechanical and thermal stimuli, as well as light, also play a role in coordinating cellular function. Receptors located in the plasma membrane, cytoplasm, and nucleus interact with these chemical and physical messengers. This interaction initiates a series of signaling events that enable cells to respond to external stimuli. These signaling pathways ensure that the cellular response to external messengers is specific, amplified, tightly regulated, and coordinated. This chapter provides a general overview of how cells communicate through external messengers and delves into the signaling pathways that process external information, leading to a well-coordinated cellular response. Subsequent chapters will delve into the details of signaling pathways in various systems such as the nervous system, muscular system, cardiovascular system, respiratory system, gastrointestinal system, renal system, and endocrine system. The importance of signaling pathways in medicine is exemplified by a list of popular drugs that regulate these pathways. More information about these pathways will be presented later in this and other chapters. For instance, aspirin, the first pharmaceutical developed in 1899, acts as an antithrombotic by inhibiting cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2), thereby reducing the formation of blood clots. β-Adrenergic receptor agonists and antagonists are used for the treatment of various medical conditions. β1-Agonists increase cardiac contractility and heart rate in patients with low blood pressure, while β2-Agonists dilate bronchi and are employed in the treatment of asthma and chronic obstructive lung disease. On the other hand, β-adrenergic antagonists are used to address hypertension, angina, cardiac arrhythmias, and congestive heart failure. Fluoxetine, an antidepressant medication also known as Prozac, enhances serotonin receptor activation by inhibiting the reuptake of serotonin into the presynaptic cell. Several monoclonal antibodies are utilized in the treatment of cancer resulting from the activation of growth factor receptors in cancer cells. Trastuzumab (Herceptin), for example, is a monoclonal antibody used to treat metastatic breast cancer in women who overexpress HER2/neu, a member of the epidermal growth factor (EGF) receptor family. These receptors stimulate cell growth and differentiation. Cetuximab (Erbitux) and bevacizumab (Avastin) are monoclonal antibodies used to treat metastatic colorectal cancer and cancers of the head and neck. These antibodies bind to and inhibit the EGF receptor, thereby impeding EGF-induced cell growth in cancer cells. Drugs that inhibit cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), are employed to prolong the vasodilatory effects of nitric oxide and treat erectile dysfunction and pulmonary arterial hypertension. An overview of cellular communication is presented in subsequent sections.
he human body is composed of billions of cells, each with a distinct function. However, the function of cells is tightly coordinated and integrated by external chemical signals, including hormones, neurotransmitters, growth factors, odorants, and products of cellular metabolism that serve as chemical messengers and provide cell-to-cell communication. Mechanical and thermal stimuli and light are physical external signals that also coordinate cellular function. Chemical and physical messengers interact with receptors located in the plasma membrane, cytoplasm, and nucleus. Interaction of these messengers with receptors initiates a cascade of signaling events that mediate the response to each stimulus. These signaling pathways ensure that the cellular response to external messengers is specific, amplified, tightly regulated, and coordinated. This chapter provides an overview of how cells communicate via external messengers and a discussion of the signaling pathways that process external information into a highly coordinated cellular response. In subsequent chapters, details on signaling pathways in the nervous system, muscular system, cardiovascular system, respiratory system, gastrointestinal system, renal system, and endocrine system are discussed in greater detail.
The significance of signaling pathways in medicine is illustrated by the following short list of popular drugs that act by regulating signaling pathways. Details on these pathways are presented later in this and other chapters.
Aspirin, the first pharmaceutical (1899), inhibits cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) and therefore is antithrombotic (i.e., reduces the formation of blood clots).
β-Adrenergic receptor agonists and antagonists are used to treat a variety of medical conditions. β1-Agonists increase cardiac contractility and heart rate in patients with low blood pressure. β2-Agonists dilate bronchi and are used to treat asthma and chronic obstructive lung disease. In contrast, β-adrenergic antagonists are used to treat hypertension, angina, cardiac arrhythmias, and congestive heart failure (see
Chapter 18).
Fluoxetine (Prozac) is an antidepressant medication that inhibits reuptake of the neurotransmitter serotonin into the presynaptic cell, which results in enhanced activation of serotonin receptors (see
Several monoclonal antibodies are used to treat cancer caused by the activation of growth factor receptors in cancer cells. For example, trastuzumab (Herceptin) is a monoclonal antibody used to treat metastatic breast cancer in women who overexpress HER2/neu, a member of the family of epidermal growth factor (EGF) receptors, which stimulate cell growth and differentiation. Cetuximab (Erbitux) and bevacizumab (Avastin) are monoclonal antibodies that are used to treat metastatic colorectal cancer and cancers of the head and neck. These antibodies bind to and inhibit the EGF receptor and thereby inhibit EGF-induced cell growth in cancer cells.
Drugs that inhibit cyclic guanosine monophosphate (cGMP)–specific phosphodiesterase type 5, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), prolong the vasodilatory effects of nitric oxide and are used to treat erectile dysfunction and pulmonary arterial hypertension (see
Chapter 17).
An overview of how cells communicate with each other is presented in