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Questions and Answers
What physiological response is associated with increased lipolysis?
What physiological response is associated with increased lipolysis?
Which of the following actions does adrenaline NOT inhibit?
Which of the following actions does adrenaline NOT inhibit?
What effect does the contraction of the splenic capsule have?
What effect does the contraction of the splenic capsule have?
Which of the following is a consequence of adrenergic sweating on palms?
Which of the following is a consequence of adrenergic sweating on palms?
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Which process is NOT stimulated by adrenaline?
Which process is NOT stimulated by adrenaline?
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What is the primary role of β1 receptors in the body?
What is the primary role of β1 receptors in the body?
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Which receptor type is involved in the process of lipolysis?
Which receptor type is involved in the process of lipolysis?
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What effect does the activation of α receptors generally have on blood vessels?
What effect does the activation of α receptors generally have on blood vessels?
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How do β2 receptors primarily affect smooth muscle in the bronchial walls?
How do β2 receptors primarily affect smooth muscle in the bronchial walls?
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What is the primary second messenger for α receptors?
What is the primary second messenger for α receptors?
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What role do β3 receptors play in body physiology?
What role do β3 receptors play in body physiology?
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Which receptor type mainly induces positive feedback inhibition in cardiovascular responses?
Which receptor type mainly induces positive feedback inhibition in cardiovascular responses?
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The activation of β receptors generally leads to what effect in the cardiovascular system?
The activation of β receptors generally leads to what effect in the cardiovascular system?
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Which neurotransmitter is primarily associated with the sympathetic nervous system?
Which neurotransmitter is primarily associated with the sympathetic nervous system?
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What percentage of adrenaline is released from the adrenal medulla?
What percentage of adrenaline is released from the adrenal medulla?
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Which of the following is NOT a synapse where noradrenaline is released?
Which of the following is NOT a synapse where noradrenaline is released?
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What is the first step in the synthesis of noradrenaline in adrenergic nerve fibers?
What is the first step in the synthesis of noradrenaline in adrenergic nerve fibers?
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Where does the synthesis of dopamine occur primarily?
Where does the synthesis of dopamine occur primarily?
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In which part of the body is adrenaline and noradrenaline stored in granules?
In which part of the body is adrenaline and noradrenaline stored in granules?
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What happens to dopamine after it is synthesized in adrenergic nerve fibers?
What happens to dopamine after it is synthesized in adrenergic nerve fibers?
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Which of the following substances has a much higher concentration in certain parts of the brain than noradrenaline?
Which of the following substances has a much higher concentration in certain parts of the brain than noradrenaline?
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What triggers the release of neurotransmitters at the axon terminal?
What triggers the release of neurotransmitters at the axon terminal?
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Which of the following describes the effect of catecholamines binding to their receptors on the postsynaptic membrane?
Which of the following describes the effect of catecholamines binding to their receptors on the postsynaptic membrane?
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What is the primary mechanism for removing catecholamines from the synaptic cleft?
What is the primary mechanism for removing catecholamines from the synaptic cleft?
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What is the role of adenyl-cyclase in adrenergic transmission?
What is the role of adenyl-cyclase in adrenergic transmission?
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Which condition leads to depolarization when catecholamines bind to their receptors?
Which condition leads to depolarization when catecholamines bind to their receptors?
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What enzyme is primarily involved in the destruction of catecholamines during neuronal uptake?
What enzyme is primarily involved in the destruction of catecholamines during neuronal uptake?
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Where is catecholamine O-methyltransferase (C.O.M.T) primarily found?
Where is catecholamine O-methyltransferase (C.O.M.T) primarily found?
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What is the difference in action between Norepinephrine and Adrenaline in adrenergic transmission?
What is the difference in action between Norepinephrine and Adrenaline in adrenergic transmission?
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Which physiological response is associated with the contraction of the bladder and gastrointestinal tract?
Which physiological response is associated with the contraction of the bladder and gastrointestinal tract?
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What effect does increased norepinephrine release have on lipolysis?
What effect does increased norepinephrine release have on lipolysis?
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Which of the following effects is associated with adrenergic sweating?
Which of the following effects is associated with adrenergic sweating?
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What is the effect of adrenaline and noradrenaline on platelet aggregation?
What is the effect of adrenaline and noradrenaline on platelet aggregation?
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Which physiological action is NOT stimulated by adrenaline based on its adrenergic activity?
Which physiological action is NOT stimulated by adrenaline based on its adrenergic activity?
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What type of receptor primarily causes vasoconstriction of blood vessels?
What type of receptor primarily causes vasoconstriction of blood vessels?
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Which of the following statements about β3 receptors is correct?
Which of the following statements about β3 receptors is correct?
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Which mechanism of action is associated with α receptors?
Which mechanism of action is associated with α receptors?
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What is the general effect of β2 receptor activation in effector organs?
What is the general effect of β2 receptor activation in effector organs?
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In terms of adrenergic transmission, which of the following is a characteristic function of α2 receptors?
In terms of adrenergic transmission, which of the following is a characteristic function of α2 receptors?
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Which of the following is a primary physiological response of β1 receptor activation in the heart?
Which of the following is a primary physiological response of β1 receptor activation in the heart?
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What secondary messenger is increased by activation of α receptors?
What secondary messenger is increased by activation of α receptors?
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Which type of adrenergic receptor is primarily located on pre-synaptic sympathetic nerve endings?
Which type of adrenergic receptor is primarily located on pre-synaptic sympathetic nerve endings?
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What effect does binding of catecholamines to postsynaptic receptors primarily have on cells?
What effect does binding of catecholamines to postsynaptic receptors primarily have on cells?
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What is the primary mechanism for the neuronal uptake of catecholamines?
What is the primary mechanism for the neuronal uptake of catecholamines?
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What is the primary consequence of stimulation of adenyl-cyclase by catecholamines?
What is the primary consequence of stimulation of adenyl-cyclase by catecholamines?
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Which part of the body is responsible for the majority of catecholamine removal?
Which part of the body is responsible for the majority of catecholamine removal?
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Which mechanism accounts for the degradation of catecholamines primarily outside of neuronal tissues?
Which mechanism accounts for the degradation of catecholamines primarily outside of neuronal tissues?
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What ionic change generally leads to hyper-polarization when catecholamines bind to their receptors?
What ionic change generally leads to hyper-polarization when catecholamines bind to their receptors?
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Which enzyme primarily contributes to the breakdown of catecholamines that are taken back into the neuron?
Which enzyme primarily contributes to the breakdown of catecholamines that are taken back into the neuron?
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What is the typical distance across the synaptic cleft that catecholamines must cross to bind to their receptors?
What is the typical distance across the synaptic cleft that catecholamines must cross to bind to their receptors?
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Which of the following best describes the storage of noradrenaline in the adrenal medulla?
Which of the following best describes the storage of noradrenaline in the adrenal medulla?
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What is the composition of catecholamines in the adrenal medulla?
What is the composition of catecholamines in the adrenal medulla?
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Which step correctly follows the conversion of DOPA in the synthesis pathway of noradrenaline?
Which step correctly follows the conversion of DOPA in the synthesis pathway of noradrenaline?
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Which of the following statements about the location of noradrenaline release is FALSE?
Which of the following statements about the location of noradrenaline release is FALSE?
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Which enzyme is primarily important for the conversion of Tyrosine into DOPA?
Which enzyme is primarily important for the conversion of Tyrosine into DOPA?
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What triggers the synthesis of dopamine in adrenergic nerve fibers?
What triggers the synthesis of dopamine in adrenergic nerve fibers?
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Which neurotransmitter is produced in much higher concentrations in specific parts of the brain compared to noradrenaline?
Which neurotransmitter is produced in much higher concentrations in specific parts of the brain compared to noradrenaline?
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Which of the following chemicals does NOT represent a step in adrenergic neurotransmission synthesis?
Which of the following chemicals does NOT represent a step in adrenergic neurotransmission synthesis?
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Study Notes
Adrenergic Receptors
- α receptors and β receptors are part of the sympathetic nervous system.
- α receptors sub-types are α1 and α2.
- β receptors sub-types are β1, β2, β3, β4, and β5.
- β3 is linked to lipolysis in adipose tissue.
- β4 and β5 are under research.
Adrenergic Transmission
- Noradrenaline is the chemical transmitter of the sympathetic nervous system.
- Noradrenaline belongs to the catecholamine group, along with adrenaline and dopamine.
- Sympathetic Post-ganglionic neurons release noradrenaline in all except sweat glands, skeletal muscle blood vessels, and sites of adrenaline release.
- Adrenal Medulla is where adrenaline (80%) and noradrenaline (40%) are released.
- Adrenaline and Noradrenaline are also released in some synapses of the CNS.
Noradrenaline Synthesis
- Synthesis begins in the cytoplasm and is completed in vesicles present in adrenergic nerve fibers.
- The synthesis process starts with phenyl-alanine, which is converted to tyrosine via hydroxylation.
- Tyrosine is converted to DOPA (Di-hydroxy phenyl-alanine) via hydroxylation.
- DOPA is then converted to Dopamine via decarboxylation.
- Dopamine is transported into vesicles of the nerve ending.
- Dopamine is converted to Noradrenaline by adding an OH group.
- In SRM and CNS neurons, Noradrenaline is further converted to adrenaline by adding a CH3 group.
Noradrenaline Storage
- Noradrenaline is mainly stored inside nerve terminals in vesicles.
- Some noradrenaline exists free in the cytoplasm.
- In adrenal medulla, adrenaline and noradrenaline are stored in the form of granules in chromaffin cells.
Noradrenaline Release
- When the action potential reaches the axon terminal, it opens voltage-gated Ca+2 channels.
- Calcium influx increases intracellular Ca2+ levels.
- Increased Ca2+ levels cause vesicles to move towards and fuse with the membrane.
- Vesicles rupture and release their contents outside the nerve fiber.
- Noradrenaline crosses the synaptic cleft (10-30 nm) and binds to its receptors on the effector organ.
- Stimulation of sympathetic preganglionic nerve fibers on chromaffin cells in the adrenal medulla causes adrenaline and noradrenaline release.
Noradrenaline Mechanism of Action
- Catecholamines bind to receptors on the postsynaptic membrane and can increase permeability to Na and Ca, or increase permeability to K and Cl.
- Increase in permeability to Na and Ca causes depolarization (stimulation).
- Increase in permeability to K and Cl causes hyperpolarization (inhibition).
- Catecholamines can also stimulate adenyl-cyclase, which converts ATP into C-AMP, initiating intracellular activities.
Noradrenaline Removal
- Noradrenaline is mainly removed by neuronal uptake (85%).
- Extra-neuronal uptake accounts for 15% of removal.
- Noradrenaline can be either stored or destroyed by the enzyme monoamine oxidase (MAO) in neuronal uptake.
- Noradrenaline is destroyed by catechol-O-methyltransferase (COMT) in extra-neuronal uptake.
- A very small amount of noradrenaline is excreted in the urine.
Noradrenaline Receptor and Action
-
α receptors are mainly excitatory.
-
β receptors are mainly inhibitory.
-
α1 receptors:
- vasoconstriction of blood vessels
- contraction of piloerector muscles
- contraction of splenic capsule
- contraction of seminal vesicle and ejaculatory duct
- contraction of bladder and GIT sphincters
- adrenergic sweating on palm
- inhibition of insulin secretion
-
α2 receptors:
- presynaptic negative feedback inhibition of noradrenaline release
- increased renin secretion
- central nervous system inhibition
-
β1 receptors:
- increased heart rate, contractility, and conduction velocity
- stimulation of liver and muscle glycogenolysis
- increased blood fibrinogen level
- peripheral platelet aggregation
-
β2 receptors:
- intestinal relaxation
- bladder relaxation
- bronchodilation
- smooth muscle relaxation in skeletal muscle blood vessels.
- smooth muscle relaxation in the bronchial wall
- smooth muscle relaxation in the bladder wall
- smooth muscle relaxation in the GIT wall
- increased lipolysis
- decreased platelet aggregation
-
β3 receptors:
- lipolysis
-
β4 and β5 receptors are under research.
-
Adrenaline and Noradrenaline are equally effective agonists for both α and β receptors.
-
Adrenaline has higher sensitivity with β receptors.
-
Noradrenaline has higher sensitivity with α receptors.
Adrenergic Receptors
- Alpha receptors: divided into alpha 1 and alpha 2 subtypes
- Beta receptors: divided into beta 1, beta 2, beta 3, beta 4, and beta 5 subtypes
- Beta 3 receptors are found in adipose tissue and are responsible for lipolysis (breakdown of fat)
- Beta 4 and beta 5 receptors are currently under research
Adrenergic Transmission
-
Alpha receptors
- Located on postsynaptic membranes of effector organs (stimulates effect)
- Located on presynaptic sympathetic nerve endings and ganglion cells (inhibits effect)
- Activation of protein G leads to increased intracellular IP3 and Ca
- Primarily excitatory:
- Vasoconstriction (narrowing of blood vessels)
- Contraction of piloerector muscles
-
Beta receptors
- Located on postsynaptic membranes of effector organs
- Activation of protein G leads to stimulation of adenyl cyclase, which increases cAMP levels
- Primarily excitatory:
- Increased cardiac properties (heart rate, contractility, conduction)
- Smooth muscle relaxation in blood vessels, bronchial walls, bladder, and gastrointestinal tract walls
- Primarily inhibitory:
- Smooth muscle relaxation
Noradrenaline
- Chemical transmitter of the sympathetic nervous system, a member of the catecholamine family (which also includes adrenaline and dopamine)
- Released from:
- All sympathetic postganglionic fibers (except sweat glands, skeletal muscle blood vessels, sites of adrenaline release)
- Adrenal medulla (80% adrenaline, 40% noradrenaline)
- Some synapses in the central nervous system (CNS)
- Synthesized in the liver through hydroxylation of phenylalanine to tyrosine
- Synthesized in the axoplasm of adrenergic nerve fibers through hydroxylation of tyrosine to DOPA (dihydroxyphenylalanine)
- Decarboxylation of DOPA produces dopamine
- Dopamine is transported into vesicles in nerve endings: hydroxylation converts dopamine into noradrenaline
- Adrenaline is formed from noradrenaline through methylation in the SRM and CNS neurons
Storage and Release of Noradrenaline and Adrenaline
- Primarily stored inside nerve terminals in vesicles
- Some are free in the cytoplasm
- In the adrenal medulla, adrenaline and noradrenaline are stored in the form of granules inside chromaffin cells
- Action potential reaches the axon terminal → opens voltage-gated Ca+2 channels → Ca2+ influx → increases Ca2+ levels → moves vesicles toward the membrane and fuses with it → vesicles rupture and release their content outside the nerve fiber → noradrenaline crosses the synapse and binds to receptors on the effector organs
- Stimulation of sympathetic preganglionic nerve fibers relaying onto chromaffin cells in the SRM causes adrenaline and noradrenaline release
Mechanism of Action of Catecholamines
- Catecholamines bind to receptors on the postsynaptic membrane, leading to:
- Increased permeability to sodium (Na) and calcium (Ca) ions
- Sodium and calcium influx → depolarization (stimulation)
- Increased permeability to potassium (K) and chloride (Cl) ions
- Potassium efflux and chloride influx → hyperpolarization (inhibition)
- Stimulation of adenyl cyclase → conversion of ATP into cAMP (which initiates intracellular activities)
Removal of Catecholamines
- Neuronal uptake: responsible for removing 85% of catecholamines; either stored or destroyed by MAO
- Extra-neuronal uptake: responsible for removing 15% of catecholamines; destroyed by COMT
- Excretion in urine: very small amount
Receptors
- Respond to adrenaline and noradrenaline
-
Alpha 1 receptors
- Increased renin secretion
- Intestinal and bladder relaxation
- Contraction of splenic capsule
- Contraction of seminal vesicle and ejaculatory duct
- Contraction of bladder and GIT sphincters
- Adrenergic sweating on the palms
- May be inhibitory
- Inhibition of insulin secretion
-
Alpha 2 receptors
-
Presynaptic
- Negative feedback inhibition of norepinephrine release
-
Postsynaptic
- Central nervous system (CNS) inhibition
- More sensitive to norepinephrine
-
Presynaptic
-
Beta 1 receptors
- Increased heart rate, contractility, and conduction
- Increased lipolysis
- Stimulation of liver and muscle glycogenolysis
- Increased blood fibrinogen levels
-
Beta 2 receptors
- Vasodilation (widening of blood vessels)
- Bronchodilation (relaxation of airways)
- Decreased platelet aggregation
- Inhibition of insulin secretion
- Intestinal relaxation
- More sensitive to adrenaline
-
Beta 3 receptors
- Located in adipose tissue
- Increased lipolysis
- Stimulation of insulin secretion
- Decreased lipolysis
- **Note: Beta 4 and Beta 5 receptors are under research ***
Agonists
- Adrenaline and Noradrenaline: equally effective on all receptors
- Adrenaline: more sensitive to beta 2 receptors
- Noradrenaline: more sensitive to alpha 2 receptors
Monoamine Oxidase (MAO)
- Located primarily in mitochondria of adrenergic fibers, liver, and kidneys
- Responsible for oxidizing catecholamines
Catechol O-Methyltransferase (COMT)
- Located in all tissues, especially the kidney and brain
- Responsible for methylating catecholamines
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