G Protein-Coupled Receptors

Definition

G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that play a crucial role in transmitting extracellular signals into intracellular responses. These receptors are involved in a wide range of physiological processes and are the target of many pharmacological agents, including the beta-adrenergic blockers discussed in Chapter 18.4.

5 Must Know Facts For Your Next Test

1. G protein-coupled receptors are the largest family of cell surface receptors, with over 800 members identified in the human genome.
2. These receptors share a common structural feature of seven transmembrane domains, which allow them to span the cell membrane and transduce extracellular signals into intracellular responses.
3. G protein-coupled receptor activation can lead to the modulation of various cellular processes, including neurotransmission, hormonal signaling, immune response, and cardiovascular function.
4. The beta-adrenergic receptors, which are targeted by beta-adrenergic blockers, are a class of G protein-coupled receptors that play a crucial role in the regulation of cardiac function and the sympathetic nervous system.
5. Dysregulation of G protein-coupled receptor signaling has been implicated in the pathogenesis of various diseases, making them an important target for pharmacological interventions.

Review Questions

• Explain the general mechanism of action of G protein-coupled receptors and how they transduce extracellular signals into intracellular responses.
  • G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that span the cell membrane with seven transmembrane domains. When an extracellular ligand binds to the receptor, it induces a conformational change that activates the associated heterotrimeric G protein. The G protein subunits then dissociate and interact with various effector proteins, such as enzymes and ion channels, to generate second messengers like cAMP and calcium. These second messengers then trigger a series of intracellular signaling cascades that ultimately result in the desired cellular response, such as changes in gene expression, metabolism, or cellular function.
• Describe the role of G protein-coupled receptors in the context of beta-adrenergic blockers and their mechanism of action in the cardiovascular system.
  • The beta-adrenergic receptors, which are a class of G protein-coupled receptors, play a crucial role in the regulation of cardiac function and the sympathetic nervous system. When stimulated by the neurotransmitter norepinephrine, the beta-adrenergic receptors activate the associated G proteins, leading to an increase in cAMP levels and subsequent activation of protein kinase A. This signaling cascade ultimately results in increased heart rate, contractility, and blood pressure. Beta-adrenergic blockers, such as those discussed in Chapter 18.4, work by competitively binding to these receptors, preventing the binding of norepinephrine and the subsequent activation of the G protein-mediated signaling pathway. This inhibition of beta-adrenergic receptor signaling leads to a reduction in heart rate, contractility, and blood pressure, making beta-adrenergic blockers an effective treatment for conditions like hypertension, angina, and heart failure.
• Analyze the importance of G protein-coupled receptor desensitization in the context of pharmacological interventions targeting these receptors, such as beta-adrenergic blockers.
  • G protein-coupled receptors can undergo a process called desensitization, in which the receptor becomes less responsive to repeated or prolonged stimulation. This is an important regulatory mechanism that helps to prevent overstimulation and maintain homeostasis within the body. In the case of beta-adrenergic receptors, desensitization can occur through receptor phosphorylation and internalization, reducing the receptor's ability to transduce the signal from the neurotransmitter norepinephrine. Pharmacological agents like beta-adrenergic blockers, which competitively bind to these receptors, can also contribute to receptor desensitization, as the continued presence of the drug prevents the receptor from being fully activated by the endogenous ligand. This desensitization process is an important consideration in the design and use of GPCR-targeted drugs, as it can impact the duration and effectiveness of the pharmacological intervention over time. Understanding the mechanisms of GPCR desensitization is crucial for optimizing the therapeutic efficacy of drugs like beta-adrenergic blockers in the treatment of cardiovascular disorders.

Related terms

Heterotrimeric G Proteins: G protein-coupled receptors are associated with heterotrimeric G proteins, which are composed of alpha, beta, and gamma subunits. Upon receptor activation, the G protein subunits dissociate and interact with various effector proteins to initiate downstream signaling cascades.

Second Messengers: G protein-coupled receptor activation leads to the generation of second messengers, such as cyclic AMP (cAMP) and calcium (Ca2+), which then trigger a series of intracellular signaling events that ultimately result in the desired cellular response.

Desensitization: G protein-coupled receptors can undergo desensitization, a process in which the receptor becomes less responsive to repeated or prolonged stimulation, often through receptor phosphorylation and internalization.