7.2 Catecholamines and the fight-or-flight response

Catecholamines are key players in the body's fight-or-flight response. These powerful molecules, including dopamine, norepinephrine, and epinephrine, are produced in specific brain regions and the adrenal glands.

When triggered, catecholamines spark a cascade of effects. They rev up the heart, boost blood flow to muscles, and sharpen our senses. This prepares us to face danger or flee from it, showcasing how hormones can rapidly alter our metabolism.

Catecholamines: Production and Sites

Major Catecholamines and Their Chemical Properties

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• Catecholamines function as neurotransmitters and hormones derived from tyrosine (an amino acid)
• Three primary catecholamines include dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline)
• Catecholamines share a common chemical structure consisting of a catechol group and an amine side chain
• These molecules play crucial roles in various physiological processes (neurotransmission, stress response, mood regulation)

Production Sites in the Body

• Dopamine originates in the substantia nigra and ventral tegmental area of the midbrain
• Norepinephrine synthesis occurs in the locus coeruleus of the pons and sympathetic nerve endings
• Epinephrine production primarily takes place in the adrenal medulla, with minor synthesis in certain brain neurons
• Chromaffin cells in the adrenal medulla produce both norepinephrine and epinephrine
• Catecholamine production sites are strategically located to facilitate rapid responses to stimuli (stress, physical activity)

Catecholamine Synthesis, Release, and Degradation

Biosynthetic Pathway

• Catecholamine synthesis initiates with tyrosine hydroxylation to form L-DOPA, catalyzed by tyrosine hydroxylase
• L-DOPA undergoes decarboxylation to dopamine via DOPA decarboxylase
• Dopamine β-hydroxylase converts dopamine to norepinephrine in noradrenergic neurons and adrenal chromaffin cells
• Phenylethanolamine N-methyltransferase (PNMT) methylates norepinephrine to form epinephrine in adrenal chromaffin cells
• This stepwise synthesis allows for the production of different catecholamines at various stages (dopamine in dopaminergic neurons, norepinephrine in noradrenergic neurons)

Storage, Release, and Degradation Mechanisms

• Catecholamines are stored in synaptic vesicles to protect them from degradation
• Release occurs through calcium-dependent exocytosis in response to neural stimulation
• Degradation primarily involves two enzymes: monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
• MAO catalyzes the oxidative deamination of catecholamines (converts norepinephrine to 3,4-dihydroxymandelic acid)
• COMT methylates the catechol group, producing metabolites like metanephrine and normetanephrine
• Reuptake mechanisms, such as the norepinephrine transporter (NET), terminate catecholamine signaling
• These processes work together to maintain appropriate catecholamine levels and prevent overstimulation

Catecholamines in the Fight-or-Flight Response

Cardiovascular and Respiratory Effects

• Fight-or-flight response activation triggers sympathetic nervous system and catecholamine release
• Catecholamines increase heart rate and contractility, enhancing cardiac output and blood flow to skeletal muscles
• Peripheral vasoconstriction redirects blood flow to critical organs and muscles (brain, heart)
• Bronchodilation improves oxygen intake and respiratory efficiency
• These cardiovascular and respiratory changes prepare the body for intense physical activity (running from a predator)

Metabolic and Cognitive Effects

• Catecholamines promote glycogenolysis in the liver and lipolysis in adipose tissue, increasing available energy substrates
• Glucose and fatty acid mobilization provides quick energy for fight-or-flight situations
• Pupil dilation (mydriasis) enhances visual acuity in low-light conditions
• Cognitive functions like attention, alertness, and sensory perception are heightened during the response
• These metabolic and cognitive changes help the body respond effectively to perceived threats (improved reaction time, increased awareness)

Adrenergic Receptors and Catecholamine Action

Receptor Classes and Subtypes

• Adrenergic receptors are G protein-coupled receptors binding catecholamines to mediate cellular effects
• Two main classes exist: alpha (α) and beta (β), each with multiple subtypes (α1, α2, β1, β2, β3)
• α1 receptors primarily locate in smooth muscle, mediating vasoconstriction and other smooth muscle contractions
• α2 receptors exist both pre- and post-synaptically, often leading to inhibitory effects (decreased neurotransmitter release)
• β1 receptors predominantly express in the heart, mediating increases in heart rate and contractility
• β2 receptors occur in various tissues, mediating bronchodilation, skeletal muscle vasodilation, and liver glycogenolysis
• Differential expression and activation of receptor subtypes contribute to diverse physiological effects during fight-or-flight response

Signaling Mechanisms and Physiological Responses

• α1 receptors couple to Gq proteins, activating phospholipase C and increasing intracellular calcium
• α2 receptors couple to Gi proteins, inhibiting adenylyl cyclase and reducing cAMP levels
• β receptors couple to Gs proteins, activating adenylyl cyclase and increasing cAMP levels
• These signaling cascades lead to various cellular responses (muscle contraction, neurotransmitter release modulation)
• Receptor distribution and density in different tissues determine the overall physiological response to catecholamines
• Understanding receptor-mediated effects aids in developing targeted therapies for conditions like hypertension and asthma