Chapter 13 - Opiods and Neuropeptides - Core concepts

Where are neuropeptides synthesized?

In the rough endoplasmic reticulum as pre-propeptides —> processed in the Golgi —> then packaged into dense-core vesicles

How do dense-core vesicles differ from small clear vesicles?

Larger, darker in EM; require higher neuronal activity for release; contain fewer transmitters but act on more sensitive receptors. 

What modifications occur in neropeptide maturation?

Cleavage, glycosylation, phosphorylation, disulfide bond formation.

Provide examples of some neuropeptides?

CCK, SOM, NPY, substance P, VIP, Enkephalin, Dynorphin

What are the three main opioid receptor types?

μ (mu), δ (delta), κ (kappa).

What G-protein do opioid receptors couple with?

Gi

What happens presynaptically when opioid receptors are activated?

↓ V-gated Ca²⁺ → ↓ neurotransmitter release

What happens post synaptically when opioid receptors are activated?

↑ GIRK channel activity → K⁺ efflux → hyperpolarization.

What is disinhibition in opioid signaling?

Opioids inhibit inhibitory interneurons, indirectly exciting pain-suppressing pathways

What causes opioid tolerance?

Receptor desensitization/internalization and compensatory neural plasticity.

Which drugs are used in opioid addiction or overdose?

• Methadone = full agonist (withdrawal relief)

• Buprenorphine = partial agonist (limits euphoria)

• Naloxone = competitive antagonist (overdose reversal)

Which has higher potency: fentanyl or morphine?

Fentanyl.

Which has higher efficacy: buprenorphine or methadone?

Methadone.

List three effects of Gi-coupled GPCR activation.

(1) Activate GIRKs → K⁺ out → hyperpolarization; (2) Inhibit V-gated Ca²⁺ channels; (3) Inhibit adenylyl cyclase.

Which receptors couple to Gi?

GABA(B), CB1, D2, α2, M2/M4 ACh, μ/δ/κ opioids, 5-HT1

Which receptors couple to Gq?

M1/M3/M5 ACh, mGluR1/5, 5-HT2, α1, CCK2.

Which receptors couple to Gs?

D1, β adrenergic, 5-HT4/6, VIP.

Why are endocannabinoids “unconventional”?

Synthesized on demand in postsynaptic cells and act retrogradely on presynaptic CB1 receptors; not stored in vesicles.

Outline 2-AG synthesis and breakdown.

PIP₂ → DAG (via PLCβ) → 2-AG (via DAGL) → degraded by MAGL → glycerol + arachidonic acid.

What effect does CB1 activation have on neurotransmission?

Inhibits Ca²⁺ channels → decreased NT release (similar to GABA B and opioid Gi pathway).

Define “potency.”

Amount of drug required to produce a given effect.

Define “efficacy.”

Maximum effect a drug can produce.

What are ionotropic receptors?

Ligand-gated ion channels causing fast responses.

What are metabotropic receptors?

GPCRs causing slower, longer-lasting responses via second messengers.

Name the main small-molecule transmitters?

Glutamate, GABA, ACh, Dopamine, Norepinephrine, Serotonin.