Cell Signalling Flashcards
Explain the difference between agonists and antagonists in pharmacology.
An agonist is a substance that emulates a messenger’s function by binding to and activating the messenger’s receptor. Conversely, an antagonist inhibits a messenger’s action by binding to and blocking the messenger’s receptors.
Referring to the provided figures, could you explain the concept of receptors? Please incorporate correct terminology like specificity, saturation, and competition in your answer.
he specific structures of both messengers and their respective receptors dictate their ability to interact with one another. This interaction is highly specific, meaning a messenger will bind to its matching receptor, setting off the receptor’s activation. Moreover, any molecule possessing a structure closely resembling that of the messenger can also potentially attach to the receptor. When competitors enter the scene, they might diminish the effectiveness of the messenger-receptor system by binding to these receptors. Seen in the graph, we see less amount of messenger bound when the competitor is present.
The specificity of these messenger-receptor interactions ensures that each messenger has a distinct function, forming the foundation for many therapeutic drugs that counteract the adverse effects of excessive naturally occurring messengers. Such drugs are referred to as antagonists.
Explain the mechanisms through which messengers physiologically regulate receptors.
Messengers can regulate receptors through two main mechanisms: up-regulation and down-regulation. Up-regulation involves an increase in the number of receptors in response to messengers, often leading to heightened sensitivity to the messenger. In contrast, down-regulation entails a reduction in the number of receptors through internalization, typically as a response to elevated extracellular levels of a messenger. These processes help maintain receptor sensitivity within an optimal range.
What are the advantages of cells expressing receptors for specific extracellular messengers, such as those related to heart rate regulation?
Cells expressing receptors for particular extracellular messengers can selectively respond to signaling molecules that are essential for their specific functions while ignoring irrelevant messengers. This selectivity ensures that the cell’s response is finely tuned to its needs. Additionally, it allows messengers to act precisely on the cells that require their effects. For instance, in the context of a messenger that enhances heart rate, it will exclusively impact cardiac tissues, ensuring a targeted response without affecting other tissues.
Explain the four classes of plasma membrane receptors and the category of messengers they interact with.
Plasma membrane receptors are specialized proteins that interact with water-soluble (hydrophilic) messengers because these messengers cannot penetrate the plasma membrane. There are four main types of receptors on the plasma membrane:
* Ligand-Gated Ion Channels: These receptors open ion channels when activated by messengers, affecting the cell’s membrane potential.
* Enzymatic Receptors: Receptors with intrinsic enzyme activity initiate cellular reactions upon messenger binding.
* Cytosolic Janus Kinase-Associated Receptors: Binding to messengers activates Janus kinases (JAKs), leading to phosphorylation of signaling molecules.
* Plasma Membrane G Protein-Linked Receptors: These receptors activate G proteins, triggering intracellular signaling cascades.
Define first messengers and second messengers.
First messengers are molecules that initially bind to cell receptors. Second messengers are substances produced within cells because of first messenger binding, amplifying the signal and initiating cellular responses.
Provide an overview of the primary second messengers, detailing their sources and effects.
Four key second messengers are vital to understand: calcium, cyclic AMP (cAMP), diacylglycerol (DAG), and inositol triphosphate (IP3).
* Calcium: Enters cells via ion channels in the plasma membrane or is released from the endoplasmic reticulum (ER) into the cytosol. Once in the cytosol, it activates various proteins, including protein kinase C and calmodulin.
* cAMP: Generated when a G protein activates plasma membrane adenylyl cyclase, which converts ATP into cAMP. cAMP, in turn, activates cAMP-dependent protein kinase (protein kinase A).
* DAG and IP3: These second messengers arise when a G protein activates plasma membrane phospholipase C, leading to their formation from plasma membrane phosphatidylinositol bisphosphate (PIP2). DAG activates protein kinase C, while IP3 induces the release of calcium from the ER into the cytosol.
Why is it advantageous to involve enzymes like adenylyl cyclase in the initial response to receptor activation by a first messenger?
Enzymes, such as adenylyl cyclase, offer several advantages. They can produce large quantities of product without being consumed themselves. One enzyme molecule can repeatedly catalyze the formation of second messengers like cAMP. Enzymes also provide a means to finely regulate their activities, allowing the cell to adjust its response to a first messenger based on various conditions and inputs.
A newly identified chemical messenger displays low solubility in water but high solubility in lipids. To which category of messengers does it likely belong? Would its actions occur more rapidly, more slowly, or at a similar pace compared to a messenger that stimulates cAMP synthesis?
This chemical messenger is probably categorized as a lipophilic messenger due to its lipid solubility. Given this characteristic, it can effectively travel across cell membranes by simple diffusion. Consequently, this messenger most likely has its receptor inside the cells, where it binds to a nuclear receptor that when activated act as a transcription factor. Examples of such messengers are steroid hormone or thyroid hormone. Such messenger act by initiating gene transcription which typically leads to slower effects compared to messengers than water-soluble (hydrophilic) messengers that causes activation of cAMP pathways.
Does a particular protein kinase, such as cAMP-dependent protein kinase, exclusively phosphorylate the same set of proteins in all cells where it’s present?
Not necessarily. While some kinases may phosphorylate the same proteins in various cell types, many cells also produce unique, cell-specific proteins that aren’t universally found. Some of these cell-specific proteins can serve as substrates for cAMP-dependent protein kinase. Consequently, the proteins targeted for phosphorylation by a specific kinase can vary depending on the cell type, resulting in tissue-specific cellular responses. For instance, in the kidneys, cAMP-dependent protein kinase phosphorylates proteins involved in inserting water channels into cell membranes, reducing urine volume. In contrast, in heart muscle cells, the same kinase phosphorylates calcium channels, enhancing muscle contraction strength.
Considering the cyclooxygenase pathway presented in the figure, what’s the rationale behind advising people to refrain from taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), all of which act as antagonists, before a surgical procedure?
Aspirin and NSAIDs inhibit the cyclooxygenase pathway, which encompasses the production of thromboxanes, as illustrated in the figure. Thromboxanes play a crucial role in blood clotting. Given the inherent risk of bleeding during any surgical procedure, using these drugs prior to surgery might heighten the chances of excessive bleeding.
