Non-adrenergic non-cholinergic transmission and co-transmission MCQs With Answer

Introduction

Non-adrenergic non-cholinergic (NANC) transmission and co-transmission are pivotal concepts in advanced pharmacology, describing neurotransmission that is neither adrenergic nor cholinergic and often involves small molecules and neuropeptides released together. This blog provides a focused set of MCQs with answers to deepen understanding of NANC mediators (e.g., nitric oxide, ATP, VIP, Substance P), their receptors, mechanisms of release, modulatory processes such as frequency-dependent co-release, and pharmacological tools used to study them. Questions emphasize molecular mechanisms, experimental approaches, and therapeutic implications in systems like gut, airway, and penile physiology, preparing M.Pharm students for rigorous examinations and practical reasoning in neuropharmacology.

Q1. What is the principal gaseous mediator commonly identified as an inhibitory NANC neurotransmitter in the gastrointestinal and vascular smooth muscle?

• Nitric oxide (NO)
• Vasoactive intestinal peptide (VIP)
• Adenosine triphosphate (ATP)
• Neuropeptide Y (NPY)

Correct Answer: Nitric oxide (NO)

Q2. Which enzyme is directly responsible for the synthesis of nitric oxide in neurons involved in NANC transmission?

• Neuronal nitric oxide synthase (nNOS)
• Inducible nitric oxide synthase (iNOS)
• Endothelial nitric oxide synthase (eNOS)
• Tyrosine hydroxylase

Correct Answer: Neuronal nitric oxide synthase (nNOS)

Q3. Co-transmission refers to which of the following phenomena at synaptic terminals?

• Simultaneous release of two or more neurotransmitters from the same neuron
• Release of neurotransmitter only after receptor internalization
• Exchange of neurotransmitters between adjacent neurons via gap junctions
• Exclusive release of a single classical transmitter per neuron

Correct Answer: Simultaneous release of two or more neurotransmitters from the same neuron

Q4. Which receptor family mediates fast excitatory purinergic responses in NANC systems?

• P2X ionotropic receptors
• P2Y metabotropic receptors
• NMDA glutamate receptors
• GABA-B receptors

Correct Answer: P2X ionotropic receptors

Q5. Which pharmacological agent is commonly used experimentally to inhibit nitric oxide synthase and thereby test NO-mediated NANC responses?

• L-NAME (Nω-Nitro-L-arginine methyl ester)
• Sodium nitroprusside
• Sildenafil
• Atropine

Correct Answer: L-NAME (Nω-Nitro-L-arginine methyl ester)

Q6. Frequency-dependent co-release implies which of the following?

• Different transmitters are preferentially released at different stimulation frequencies
• All transmitters are released equally regardless of frequency
• Release depends solely on action potential amplitude, not frequency
• Only peptides are released at low frequency

Correct Answer: Different transmitters are preferentially released at different stimulation frequencies

Q7. Which neuropeptide is typically associated with excitatory NANC transmission and often causes smooth muscle contraction in the gut?

• Substance P
• Vasoactive intestinal peptide (VIP)
• Nitric oxide (NO)
• Galanin

Correct Answer: Substance P

Q8. Ectonucleotidases in the synaptic cleft primarily influence NANC signaling by doing what?

• Hydrolyzing extracellular ATP to adenosine, thereby terminating/potentiating purinergic signals
• Synthesizing ATP from ADP to prolong purinergic transmission
• Transporting neuropeptides back into presynaptic terminals
• Phosphorylating receptors to increase sensitivity

Correct Answer: Hydrolyzing extracellular ATP to adenosine, thereby terminating/potentiating purinergic signals

Q9. Which statement best describes Dale’s principle as revised in the context of co-transmission?

• A neuron can release multiple neurotransmitters, though not necessarily all at the same time
• Each neuron releases only one neurotransmitter universally
• Neurons must always release neurotransmitters in equal proportions
• Neurons release transmitters only during development

Correct Answer: A neuron can release multiple neurotransmitters, though not necessarily all at the same time

Q10. Which technique is most appropriate for confirming co-localization of two neurotransmitters within the same nerve terminal?

• Immunohistochemistry with confocal microscopy
• Radioligand binding assays on whole tissue homogenates
• Microdialysis without subsequent analysis
• Patch clamp recording from postsynaptic cells only

Correct Answer: Immunohistochemistry with confocal microscopy

Q11. In erectile physiology, which NANC mediator is primarily responsible for smooth muscle relaxation leading to penile erection?

• Nitric oxide (NO)
• Substance P
• Adenosine triphosphate (ATP)
• Norepinephrine

Correct Answer: Nitric oxide (NO)

Q12. Which co-transmitted molecule often modulates the effect of NO by acting on smooth muscle cyclic GMP pathways through phosphodiesterase inhibition clinically?

• Sildenafil (PDE5 inhibitor) potentiates NO-cGMP signaling
• Atropine blocks muscarinic potentiation of NO
• L-NAME enhances NO production
• Propranolol increases NO degradation

Correct Answer: Sildenafil (PDE5 inhibitor) potentiates NO-cGMP signaling

Q13. Prejunctional heteroreceptors in NANC nerves typically regulate transmitter release by responding to what?

• Neurotransmitters released from neighboring neurons or non-neuronal cells
• Only the postsynaptic membrane potential
• Direct binding of intracellular G-proteins
• Changes in extracellular pH exclusively

Correct Answer: Neurotransmitters released from neighboring neurons or non-neuronal cells

Q14. Which peptide is commonly co-released with acetylcholine in enteric neurons and produces inhibitory effects on gut motility?

• Vasoactive intestinal peptide (VIP)
• Substance P
• Glutamate
• Calcitonin gene-related peptide (CGRP)

Correct Answer: Vasoactive intestinal peptide (VIP)

Q15. Which of the following is a hallmark experimental finding that suggests NANC inhibitory transmission in isolated smooth muscle strips?

• Relaxation persisting after blockade of adrenergic and cholinergic receptors
• Contraction blocked by muscarinic antagonists
• Responses abolished by beta-adrenoceptor blockers only
• No change after nitric oxide synthase inhibition

Correct Answer: Relaxation persisting after blockade of adrenergic and cholinergic receptors

Q16. Which calcium sensor protein is implicated in differential release of small molecule transmitters versus neuropeptides during co-transmission?

• Synaptotagmin isoforms (e.g., synaptotagmin-1 vs synaptotagmin-7)
• Calmodulin exclusively for neuropeptides
• Cyclophilin for small molecules only
• GAP-43 as the sole release trigger

Correct Answer: Synaptotagmin isoforms (e.g., synaptotagmin-1 vs synaptotagmin-7)

Q17. Which receptor class mediates the slow metabotropic responses to ATP in many NANC pathways?

• P2Y G-protein coupled receptors
• P2X ligand-gated ion channels
• mACh muscarinic receptors
• Ionotropic glutamate receptors

Correct Answer: P2Y G-protein coupled receptors

Q18. In disorders like achalasia or diabetic gastroparesis, impairment of which NANC mediator pathway is most commonly implicated?

• Nitric oxide-mediated inhibitory enteric transmission
• Overactive adrenergic transmission
• Excessive cholinergic excitatory input only
• Dysregulated GABAergic transmission

Correct Answer: Nitric oxide-mediated inhibitory enteric transmission

Q19. Which technique allows real-time measurement of NANC neurotransmitter release from nerve terminals in vitro?

• Fast-scan cyclic voltammetry or enzyme-linked biosensors for specific mediators
• Western blotting of whole tissue immediately after stimulation
• Electron microscopy of fixed samples
• Single-point spectrophotometry without sampling extracellular fluid

Correct Answer: Fast-scan cyclic voltammetry or enzyme-linked biosensors for specific mediators

Q20. Which therapeutic strategy targets NANC pathways to treat pulmonary hypertension by enhancing NO signaling?

• Use of phosphodiesterase-5 inhibitors and inhaled NO donors
• Administration of muscarinic agonists
• Beta-2 adrenergic antagonists
• Peripheral alpha-1 adrenergic agonists

Correct Answer: Use of phosphodiesterase-5 inhibitors and inhaled NO donors

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