Chapter 6: Communication, Integration, and Homeostasis
Cell-to-Cell Communication
Physiological signals include:
Electrical signals:
Changes in the membrane potential of a cell.
Chemical signals:
Secreted by cells into extracellular fluid (ECF).
Responsible for most communication within the body.
Chemical signals are also known as ligands.
Target cells (targets) respond to signals.
Protein binding of chemical signals:
Specificity: The ability of a receptor to respond to particular ligands.
Affinity: The strength of the bond between ligand and receptor.
Competition: When multiple ligands compete for the same receptor.
Saturation: Refers to the point at which all receptors are occupied by ligands, and no additional response can be elicited.
Local Communication
Methods of local cell communication:
Gap junctions create cytoplasmic bridges.
Contact-dependent signals require cell-to-cell contacts.
Chemicals diffuse through extracellular fluid to act on nearby cells.
Long-distance communication uses chemical and electrical signals.
Long-Distance Communication
Modes of long-distance communication include chemical and electrical signals, such as:
Hormones.
Neurocrines:
Chemical signals secreted by neurons which include:
Neurotransmitters (fast-acting.)
Neuromodulators (modulate neurotransmitter action.)
Neurohormones (released into the blood.)
Cytokines: Local and Long-Distance Signals
Cytokines are peptides synthesized and secreted by all nucleated cells in response to stimuli.
Cytokine Families include: interferons, interleukins, colony-stimulating factors, growth factors, tumor necrosis factors, chemokines.
In development and differentiation, usually function as autocrine or paracrine signals.
In stress and inflammation, some may act on relatively distant targets.
Differences from classical hormones:
Any nucleated cell can produce them vs. only specialized epithelial cells can produce hormones.
Cytokines are made on demand vs. hormones made in advance and stored.
Intracellular pathways differ from those of hormones.
Signal Pathways
Receptor proteins:
A target cell responds to a specific chemical signal only if the cell has a corresponding receptor.
The Signal Pathway includes:
The chemical signal (first messenger) is a ligand that binds to the receptor protein.
Ligand-receptor binding activates the receptor.
The receptor activates one or more intracellular signal molecules.
The last signal molecule modifies existing proteins or initiates the synthesis of new proteins.
Receptor Locations
Receptors are located either inside the cell or on the cell membrane.
Lipophilic and Lipophobic Signal Molecules
Lipophilic signal molecules:
Can diffuse through the cell membrane.
Usually bind to cytosolic receptors or nuclear receptors.
Lipophobic signal molecules:
Bind to receptors on the cell membrane.
Categories of Membrane Receptors
Four categories include:
Chemically gated (ligand-gated) ion channels (receptor-channels).
G protein-coupled receptors (GPCR).
Receptor-enzymes.
Integrin receptors.
Signal Transduction
Signal transduction refers to the process of converting a signal from one form to another.
The extracellular signal is considered the first messenger, while intracellular signals are second messengers that alter signaling pathways.
Key Processes in Signal Transduction:
Activation of amplifier enzymes and protein kinases.
Altering gating of ion channels.
Increasing intracellular calcium levels.
Changing enzyme activity, such as with protein phosphatases.
Cascades of activation steps allow for signal amplification, whereby one ligand can generate many intracellular responses.
Second Messenger Pathways and Effects
Second messengers include:
cAMP (cyclic AMP): Produced from ATP by adenylyl cyclase and activates protein kinase A.
cGMP (cyclic GMP): Produced by guanylyl cyclase and has various regulatory roles.
IP3 (inositol trisphosphate) and DAG (diacylglycerol): Role in calcium release and protein kinase C activation.
Ion Channels in Signal Pathways
Most rapid signal pathways involve changes in ion flow through channels primarily in nerve and muscle tissues.
Mechanism:
Ligand binding to a receptor-channel alters cell permeability, allowing rapid ion movement and immediate cellular response.
G Protein-Coupled Receptors (GPCR) and Signal Transduction
GPCRs: Cytoplasmic tail linked to G proteins, which are three-part transducer molecules.
Common pathways include the adenylyl cyclase-cAMP system and pathways linked to phospholipase C, which lead to multiple second messengers.
Catalytic Receptors
Receptor-enzymes act by ligand binding activating intracellular enzymes.
Examples include:
Protein kinases: (e.g., tyrosine kinase).
Guanylyl cyclase: Converts GTP to cyclic GMP (cGMP).
Integrin Receptors
Integrins are membrane-spanning proteins; they bind to extracellular matrix proteins outside of the cell while attaching to the cytoskeleton inside via anchor proteins.
Novel Signal Molecules
Role of Calcium as an Intracellular Signal
Calcium is an important intracellular signal that can enter through gated channels or be released from intracellular compartments.
It binds to regulatory proteins like calmodulin to elicit a cellular response.
Gases as Ephemeral Signal Molecules
Nitric oxide (NO):
A short-acting paracrine or autocrine produced by endothelial cells causing vasodilation.
Synthesized through nitric oxide synthase (NOS) and activates guanylyl cyclase to produce cGMP.
Acts also as a neurotransmitter and neuromodulator in the brain.
Carbon monoxide (CO):
Activates guanylyl cyclase and cGMP, targeting smooth muscle and neural tissue.
Hydrogen sulfide:
Targets the cardiovascular system to relax blood vessels, with garlic being a principal dietary source.
Lipid Signaling Molecules
Eicosanoids derived from arachidonic acid act as lipid signaling molecules, engaging GPCRs and produced from membrane phospholipids through the action of phospholipase A2 (PLA2).
Leukotrienes are implicated in asthma and anaphylactic responses.
Prostanoids:
Composed of prostaglandins and thromboxanes, play roles in sleep, inflammation, pain, and fever. Nonsteroidal anti-inflammatory drugs (NSAIDs) block cyclooxygenase (COX) to reduce inflammation.
Sphingolipids are involved in regulating inflammation, cell adhesion, growth, and death.
Modulation of Signal Pathways
Receptor Agonists and Antagonists:
An agonist activates a receptor, producing a response.
An antagonist blocks receptor activity, inhibiting response.
Target Response:
Depends on the target receptor.
Abnormal Signaling Mechanisms
Table 6.1 lists some diseases linked to abnormal signaling pathways, such as genetically inherited receptor malfunctions and toxins affecting signal pathways like Bordetella pertussis toxin, which keeps adenylyl cyclase active, causing disruptions in normal function.
Homeostatic Reflex Pathways
Cannon’s Postulates: Describe regulated variables and control systems governing internal environments.
Nervous Regulation of Internal Environment:
Key control mechanisms include:
Tonic control: Continuous regulation, such as vascular tone.
Antagonistic control: Opposing actions of signals regulating a parameter.
A single chemical signal may have diverse effects depending on tissue type.
Reflex Pathways and Feedback Loop
Components of long-distance reflex pathways include:
Input: Stimulus and sensor/receptor pathways.
Integration: Integrated by a center that compares responses to setpoints.
Output: Involves an output signal to a target or effector leading to a response.
Reflex Steps Illustrated
The input phase gathers signals; integration compares those signals against setpoints, and output generates responses based on that processing.
Control Systems Variability
Reflexes mediated by the nervous system are typically faster and more specific compared to those mediated by the endocrine system, which tend to be slower and more generalized.
Differences in Neural and Endocrine Control
Comparison Table 6.2 outlines the differences in specificity, speed, and duration of action between neural reflexes that are rapid and highly specific, and endocrine reflexes that are chemical and widespread but slower in response.