[PCOL] 2.2 Sympathetic Nervous System (Introduction)

Which G-protein and secondary messengers are coupled to the alpha1 receptor?

A. Gs; increase cAMP

B. Gq; increase IP3, DAG

C. Gi; decrease cAMP

D. Gs; decrease IP3, DAG

B. Gq; increase IP3, DAG

Explanation: The alpha1 receptor is coupled to Gq which activates Phospholipase C (PLC) to produce IP3 and DAG. This cascade ultimately leads to an increase in intracellular Ca2+ and subsequent cell Contraction (e.g.,smooth muscle).

The major function of alpha1 receptor stimulation in Vascular Smooth Muscle (Cutaneous splanchnic) is:

A. Vasodilation

B. Decrease in BP

C. Vasoconstriction

D. Increased secretion

C. Vasoconstriction

Explanation: alpha1 stimulation causes smooth muscle contraction. In blood vessels like Cutaneous splanchnic (skin and abdominal organs), this leads to Vasoconstriction, resulting in increased Peripheral Resistance and BP.

Stimulation of alpha1 receptors in the Radial muscle of the iris causes what visible effect on the pupil?

A. Miosis (constriction)

B. Cycloplegia (blurring of vision)

C. Mydriasis (dilation of pupil)

D. Lacrimation

C. Mydriasis (dilation of pupil)

Explanation: The Radial muscle is the Dilator Pupillae. alpha1 stimulation causes its Contraction, leading to pupil Dilation (Mydriasis).

Which G-protein and change in cAMP are associated with the alpha2 receptor?

A. Gq; increase cAMP

B. Gi; decrease cAMP

C. Gs; increase cAMP

D. Gq; decrease IP3

B. Gi; decrease cAMP

Explanation: The alpha2 receptor is typically coupled to Gi (inhibitory), which inhibits adenylyl cyclase and leads to a decrease in cAMP.

What is the major functional effect of stimulating alpha2 receptors when they are located on the Presynapse (Autoregulation)?

A. Increase release of NE

B. Vasoconstriction

C. Inhibition of further NE release (anti-sympathetic)

D. Increased BP

C. Inhibition of further NE release (anti-sympathetic)

Explanation: Presynaptic alpha2 receptors act as Autoreceptors. When stimulated, they activate the Gi pathway, leading to Autoregulation which inhibits further release of NE, causing an anti-sympathetic effect (e.g., used for sedation, and blood pressure control).

Which Beta receptor is found primarily on Cardiac Muscle and mediates the positive chronotropism, inotropism, and dromotropism of the heart?

A. beta3

B. beta2

C. beta1

D. alpha1

C. beta1

Explanation: The beta1 receptor is predominantly found on Cardiac Muscle. It is coupled to Gs (increase cAMP) and mediates the heart's (+) chronotropism (HR), (+) inotropism (contractility), and (+) dromotropism (conduction velocity).

beta1 receptor stimulation in the Juxtaglomerular Apparatus (Kidney) leads to what major functional outcome?

A. Decrease Renin release

B. Diuresis (water loss)

C. Increase Renin release (increase BP)

D. Hypokalemia

C. Increase Renin release (increase BP)

Explanation: The beta1 receptor on Juxtaglomerular cells is a major mechanism for Renin release. This activates the RAAS (Renin-Angiotensin-Aldosterone System) which ultimately leads to an increase in BP.

What is the major functional effect of beta2 receptor stimulation on the Bronchi Smooth Muscle?

A. Bronchoconstriction

B. Contraction

C. Relaxation (bronchodilation)

D. Increased secretion

C. Relaxation (bronchodilation)

Explanation: beta2 receptors, coupled to Gs (increase cAMP), cause Smooth Muscle Relaxation. In the Bronchi, this leads to Bronchodilation, which is the target of beta2 agonists in asthma treatment.

beta2 receptor stimulation in Skeletal Muscle can cause which electrolyte disturbance?

A. Hyperglycemia

B. Hyperkalemia

C. Hypokalemia

D. Hyponatremia

C. Hypokalemia

Explanation: beta2 receptors in Skeletal Muscle regulate intracellular uptake movement of K+ ions. Stimulation causes K+ to shift into the cells, which can lead to Hypokalemia (low K+ in the blood).

Which Beta receptor is found primarily on Adipose Cells and mediates Lipolysis?

A. beta1

B. beta2

C. beta3

D. alpha2

C. beta3

Explanation: The beta3 receptor is coupled to Gs (increase cAMP) and is located on Adipose Cells, where its stimulation leads to Lipolysis (breakdown of fat for energy).

beta2 receptor stimulation in the Uterus causes what major effect, sometimes utilized as a therapeutic goal?

A. Uterine contraction

B. Increased uterine tone

C. Uterine relaxation / tocolysis

D. Uterine vasoconstriction

C. Uterine relaxation / tocolysis

Explanation: beta2 receptor stimulation causes smooth muscle Relaxation. In the Uterus, this effect is Uterine relaxation (Tocolysis), which is used clinically to suppress premature labor.

Glycogenolysis leading to an increase in glucose level is a metabolic effect mediated by which receptor located in the Liver?

A. alpha1

B. beta2

C. beta1

D. alpha2

B. beta2

Explanation: beta2 receptor stimulation in the Liver initiates Glycogenolysis (breaking down stored glycogen) and gluconeogenesis, which contribute to an increase in blood glucose level (Hyperglycemia).

Which G-protein and secondary messenger system are coupled to the D1 receptor?

A. Gi; decrease cAMP

B. Gq; increase IP3 and DAG

C. Gs; increase cAMP

D. Gi; increase cAMP

C. Gs; increase cAMP

Explanation: The D1 receptor, like beta1 and beta2 receptors, is coupled to Gs (stimulatory G-protein), which activates adenylyl cyclase to cause an increase in cAMP.

D1 receptor stimulation in the Renal Vasculature and Splanchnic Blood Vessels causes what major effect?

A. Vasoconstriction

B. Increased BP

C. Vasodilation

D. Decreased GFR

C. Vasodilation

Explanation: D1 receptor stimulation causes Vasodilation in these peripheral vascular beds. This effect leads to an increase in GFR (Glomerular Filtration Rate) and diuresis (urine production), which in turn lowers BP (Diuresis =decrease BP).

Which Peripheral Dopaminergic receptor is coupled to the Gi protein?

A. D1

B. D2

C. D3

D. D4

B. D2

Explanation: The D2 receptor is coupled to Gi (inhibitory G-protein), which inhibits adenylyl cyclase and leads to a decrease in cAMP.

Stimulation of the Peripheral D2 receptor in the Gastrointestinal Tract causes what effect?

A. Increased motility

B. Diarrhea

C. Decrease GIT motility (Constipation / Ileus)

D. Increased secretion

C. Decrease GIT motility (Constipation / Ileus)

Explanation: Peripheral D2 activation, coupled to the inhibitory Gi pathway, leads to decreased GIT motility (loss of peristalsis / ileus), clinically resulting in Constipation.

Which group of Dopaminergic receptors (D2, D3, D4) are located in the Central Nervous System (CNS) and coupled to the Gs G-protein, leading to an increase in cAMP?

A. D1

B. D2, D3, D4

C. D1, D5

D. D3 only

B. D2, D3, D4

Explanation: The Central D2, D3, and D4 receptors are listed together as being coupled to Gs (increase cAMP) in the CNS. (Note: While D2 is classically Gi-coupled, the notes list its CNS effects with D3 and D4 as Gs coupled, mediating functions like Behavioral changes, Perception regulation, and Modulation of motor activities).

What is the precursor amino acid for the biosynthesis of all catecholamines (NE, Epi, Dopa)?

A. Tryptophan

B. Tyrosine

C. Serine

D. Phenylalanine

B. Tyrosine

Explanation: The biosynthesis process begins with the Active uptake of tyrosine into the nerve terminal or chromaffin cell.

What is the rate limiting step in the biosynthesis of catecholamines, and which enzyme catalyzes it?

A. Formation of Dopamine; DOPA decarboxylase

B. Formation of Epinephrine; PENMT

C. Conversion of tyrosine to L-DOPA; Tyrosine hydroxylase

D. Formation of NE; Dopamine-beta-hydroxylase

C. Conversion of tyrosine to L-DOPA; Tyrosine hydroxylase

Explanation: The conversion of Tyrosine to L-DOPA by Tyrosine hydroxylase is the Rate limiting step of the entire pathway.

Which drug is an inhibitor of Tyrosine hydroxylase and thereby inhibits the formation of L-DOPA?

A. Carbidopa

B. Reserpine

C. Guanethidine

D. Metyrosine

D. Metyrosine

Explanation: Metyrosine (Inhibitor) blocks the Rate limiting step of Tyrosine hydroxylase.

Which enzyme catalyzes the Formation of the first catecholamine (Dopamine) from L-DOPA?

A. Tyrosine hydroxylase

B. DOPA decarboxylase

C. Dopamine-beta-hydroxylase

D. PENMT

B. DOPA decarboxylase

Explanation: L-DOPA is converted to Dopamine by the enzyme DOPA decarboxylase.

The formation of Norepinephrine (NE) occurs inside the vesicle and is catalyzed by which enzyme?

A. Tyrosine hydroxylase

B. DOPA decarboxylase

C. Dopamine-beta-hydroxylase

D. PENMT

C. Dopamine-beta-hydroxylase

Explanation: Dopamine (DA) is converted to Norepinephrine (NE) by Dopamine-beta-hydroxylase (DBH) inside the storage vesicle.

Which organ is the primary Site for the final step, the Formation of Epinephrine?

A. Brain / CNS

B. Postganglionic sympathetic nerves

C. Kidney (Juxtaglomerular apparatus)

D. Adrenal medulla

D. Adrenal medulla

Explanation: The conversion of Norepinephrine to Epinephrine by PENMT (Phenylethanolamine methyltransferase) occurs almost exclusively in the Adrenal medulla, where Epinephrine is released as a hormone.

The drug Reserpine and Tetrabenazine inhibit which step of catecholamine neuronal transmission?

A. Formation of L-Dopa

B. Release of NE into cleft

C. Vesicular Storage and uptake of Dopamine

D. Neuronal Reuptake

C. Vesicular Storage and uptake of Dopamine

Explanation: Reserpine is an inhibitor of the VMAT (Vesicular monoamine transporter), preventing the Vesicular storage of dopamine and its subsequent conversion to NE, leading to the premature breakdown and depletion of catecholamines.

What is the essential ion required for the Exocytotic release of neurotransmitters into the synaptic cleft?

A. Sodium ion (Na+)

B. Potassium ion (K+)

C. Chloride ion (Cl−)

D. Calcium ion (Ca2+)

D. Calcium ion (Ca2+)

Explanation: Exocytotic release of NTs is a Ca2+-dependent process. Ca2+ influx into the presynapse is the trigger for vesicle fusion and release.

Which drug mechanism is responsible for the inhibition of Neuronal Reuptake of NE?

A. TCA (Tricyclic Antidepressants), Cocaine, NARI (Norepinephrine Reuptake Inhibitors)

B. Guanethidine, Guanadrel, Bretylium

C. Reserpine, Tetrabenazine

D. Metyrosine

A. TCA (Tricyclic Antidepressants), Cocaine, NARI (Norepinephrine Reuptake Inhibitors)

Explanation: The Reuptake of NE from the synaptic cleft is the major mechanism of NT termination. Drugs like TCA and Cocaine block this reuptake, prolonging NE's action.

Which drug, a potent Stimulant of NT release, is an indole alkaloid that causes an explosive release of catecholamines?

A. Tyramine

B. Amphetamine

C. alpha-latrotoxin (from black widow spider)

D. Ephedrine

C. alpha-latrotoxin (from black widow spider)

Explanation: alpha-latrotoxin is specifically listed as a Stimulant that causes an explosive release of catecholamines and is derived from the black widow spider.

The three possible fates of a neurotransmitter (NT) in the synaptic cleft are: Binding on post-synaptic receptors, Metabolism, and Reuptake. Which of these is the Major mechanism for termination of activity (approx 70%)?

A. Binding on post-synaptic receptors

B. Metabolism by MAO/COMT

C. Reuptake into the synapse

D. Exocytotic release

C. Reuptake into the synapse

Explanation: Reuptake into the synapse via transporters is the Major mechanism for termination of activity (70%) for most NTs like NE.

Reuptake of NTs is carried out by which specialized transporter located in the pre-synapse?

A. VMAT (Vesicular Monoamine Transporter)

B. DOPA decarboxylase

C. NE Transporter / Uptake-1 Transporter

D. GABA Transporter

C. NE Transporter / Uptake-1 Transporter

Explanation: The NT carrier responsible for reuptake into the pre-synapse is the NE Transporter (or Uptake-1 Transporter), which moves the NT back into the neuron.

What is the immediate effect of NT reuptake on the remaining NT?

A. Accelerates NT metabolism

B. Prevents premature metabolism

C. Increases post-synaptic binding

D. Increases Ca2+ influx

B. Prevents premature metabolism

Explanation: By moving the NT back into the pre-synapse, the reuptake mechanism prevents premature metabolism that would otherwise occur in the synaptic cleft.

The neurotransmitters are metabolized in the synaptic cleft primarily by which two enzymes?

A. MAO (Monoamine Oxidase) and COMT (Catechol-O-methyltransferase)

B. DOPA decarboxylase and DBH

C. Tyrosine hydroxylase and PENMT

D. AChE (Acetylcholinesterase) and COMT

A. MAO (Monoamine Oxidase) and COMT (Catechol-O-methyltransferase)

Explanation: Metabolism is one of the fates of NTs and is carried out by MAO and COMT, which break down the Catecholamines.

TCAs (Tricyclic Antidepressants) primarily inhibit the reuptake of which two NTs?

A. ACh > Dopamine

B. Epi > Serotonin

C. NE > 5-HT (Serotonin)

D. GABA > Glutamate

C. NE > 5-HT (Serotonin)

Explanation: TCAs are listed as Reuptake Inhibitors with a preferential effect on NE (Norepinephrine) over 5-HT (Serotonin) (NE > 5-HT).

The combined use of TCAs (inhibits reuptake) and MAOIs (inhibits metabolism) is contraindicated due to the risk of:

A. Serotonin Syndrome

B. Severe Sedation

C. Hypertensive Crisis

D. Hypoglycemia

C. Hypertensive Crisis

Explanation: The NOTES explicitly warn that the combination leads to the Accumulation of catecholamines (NE levels spike because both elimination pathways are blocked), resulting in a Hypertensive Crisis.

Which drug, a NE Reuptake Inhibitor, is known to cause vasoconstriction?

A. Sibutramine

B. Atomoxetine

C. Reboxetine

D. Cocaine

D. Cocaine

Explanation: Cocaine is listed as an Inhibitor of Reuptake and is noted to cause vasoconstriction (by acutely increasing NE levels), which can lead to cardiovascular toxicity.

Reboxetine, Sibutramine, and Atomoxetine are examples of which class of drugs?

A. MAO Inhibitors

B. VMAT Inhibitors

C. DOPA Decarboxylase Inhibitors

D. NE Reuptake Inhibitors (NARI)

D. NE Reuptake Inhibitors (NARI)

Explanation: These three drugs are explicitly listed as Inhibitors under the NE Reuptake Inh category. Atomoxetine is used for ADHD, Reboxetine for depression, and Sibutramine was used for weight loss.