[03-PRE-PCOL] RECEPTOR AND TYPE OF RECEPTORS

Receptor

Functional macromolecular cell components with specific stereochemical configuration where ligand interacts usually in lock & key fashion.

Highly specific/selective

The stereochemical configuration of receptor is?

Lock-and-key fashion

The ligands interact in a?

• Lock (receptor)

• Key (drug)

In a lock-and-key fashion, which is the receptor and the drug?

Ligands

The receptor binds with specific structure of?

Ligands

This actively binds with the receptor.

• Neurotransmitters

• Hormones

• Autacoids

What are the three (3) examples of endogenous substances?

• Norepinephrine

• Acetylcholine

• Glutamate

• Serotonin

What are the four (4) examples of neurotransmitters that are excitatory?

Excitatory neurotransmitter

These neurotransmitter facilitates transmission of signal.

• GABA

• Glycine

What are the two (2) examples of neurotransmitters that are inhibitory?

Gamma-aminobutyric acid (GABA)

It is the main neurotransmitter in the brain.

Brain

GABA is the main NT in?

Glycine

It is the main neurotransmitter in the spinal cord.

Spinal cord

Glycine is the main NT in?

Local hormones

Autacoids is also known as?

Exogenous Compounds/Ligands

These drugs has the same structure with receptor and it act as activators or blockers; depending in signal.

Stereochemical configuration

Receptor as the lock is highly selective and specific with?

Drug-Receptor Complex

When the drug and the receptor binds, it will form?

Drug-Receptor Complex

This complex induces or elicits effect/response.

Proportional

The magnitude of response is __________ to the number of drug-receptor complex.

The more effect produced

The more receptor binds to ligand, the more?

Protein-targeting

The major receptor families are also considered as?

Voltage-gated Ion Channels

This channel opens when there is voltage.

Ligand-gated Ion Channels

This channel responds to a binding ligand.

Ligand-gated Ion Channels

Major Receptor Families:

Type I or Ionotropic Receptors is also known as?

Cell membrane

Where is the location of Type 1: Ligand-gated Ion Channels (Ionotropic Receptors) which take effect at milliseconds.

Nicotinic acetylcholine receptors

Type 1: Ligand-gated Ion Channels (Ionotropic Receptors):

This drug is coupled with Na⁺ channels.

1. Acetylcholine

2. Nicotinic receptor

In order to open the channel, the ligand in a form of (1)_____ must bind to the (2)__________ to cause a flux of sodium ion.

Acetylcholine

Type 1 receptor opens in the response to the nicotinic’s binding ligand called?

• Nicotinic acetylcholine receptors

• GABA_A receptors

• Glycine receptors

• Serotonin (5-HT₃) receptors

What are the four (4) examples of drugs under Type 1: Ligand-gated Ion Channels?

Cl^- channels

GABA_A receptors is bind with what channel?

GABA

In GABA_A, which is the binding ligand?

Cl^- channels

Glycine is coupled with what channel?

Glycine

In glycine receptor, which one is the binding ligand?

5-HT₃

Serotonin receptors is also known as?

Na⁺ channel

Serotonin (5-HT₃) receptors is coupled with what channel?

Serotonin

Serotonin (5-HT₃) receptors which is the binding ligand?

In the postrema of the brain

Serotonin (5-HT₃) receptors is located where?

Postrema of Brain

Where is the chemoreceptor trigger zone located?

Chemotherapy

Chemoreceptor trigger zone will be triggered if the patient undergo?

Nausea and vomitting

When the chemoreceptor trigger zone is triggered it will induce?

Anti-emetic (blocks 5-HT)

As a remedy, the doctors will give the patient an ________________ before undergoing chemotherapy to reduce nausea and vomiting.

• Nicotine

• Lobeline

• Varenicline

• Acetylcholine

What are the four (4) activators of Nicotinic Receptors?

Tubocurarine (neuromuscular blockers)

What are the blocker of Nicotinic Receptors?

• Benzodiazepines

• Barbiturates

What are the two (2) activators of GABA_A receptors?

Strychnine

What is the blocker for glycine receptors?

-setron

What is the blocker in serotonin (5-HT₃) receptors?

Metabotropic Receptors

Type 2: G-Protein Coupled Receptors is also known as?

Cell membrane

Where is the Type 2: G-Protein Coupled Receptors located?

Seconds

What is the onset of response of action of Type 2: G-Protein Coupled Receptors?

G-protein

In Type 2: G-Protein Coupled Receptors, what is the protein attached to the receptor?

Secondary messengers

Before producing an effect, Type 2: G-Protein Coupled Receptors, will release a?

• cAMP (Cyclic Adenosine Monophosphate)

• cGMP (Cyclic Guanosine Monophosphate)

• IP₃ (Inositol Triphosphate)

• DAG (Diacylglycerol)

What are the four (4) secondary messengers (they are small molecules or ions transmitting signals from the receptor towards effector organ before producing biologic effects)?

1. Diverse

2. Isolated

cAMP and cGMP has the same signal but cAMP is more (1)_____ an cGMP is more (2)_____?

Vascular smooth muscles or intestinal mucosa

The cGMP is isolated mostly on the?

Intracellular calcium ion channel

When the IP₃ and DAG is released, they will enhance the?

Muscular contraction

When the IP₃ and DAG enhanced the intracellular calcium ion channel, there will be a?

• Gs

• Gi

• Gq

What are the three (3) types of G-Protein?

Gs

This G-protein stimulates adenylyl cyclase producing cAMP.

• Epinephrine

• Norepinephrine

• Salbutamol

What are the drugs that activates the beta-receptors Gs protein?

• Metoprolol

• Atenolol

• Propranolol

• Nebivilol

• Carvedilol

What are the drugs that blocks the beta-receptors Gs protein?

Beta-blockers (cardiovascular drugs)

-olol drugs are?

Beta-receptors

These receptors increases heart rate, contractility.

• B-receptors

• Dopamine-1 receptor

• Histamine (H₂) receptor

What are the examples of Gs protein?

Fenoldopam (agonist)

Example of dopamine-1 receptor which is an anti-hypertensive; renal vasodilation = low BP

Famotidine (antagonist)

Examples of Histamine (H₂) Receptor that lowers gastric acid secretion; Kremil-S Advance.

Gi

This G-protein inhibits adenylyl cyclase = lower cAMP, higher cGMP

• Dopamine (D₂)-receptors

• Muscarinix (M₂)-receptors

• Pre-synaptic a₂-receptors

What are the examples of Gi proteins?

Antipsychotics

What is an example of drug that targets Dopamine (D₂)-receptors?

Anticholinergics

What is an example of drug that targets Muscarinic (M₂)-receptors?

Atropine

This anticholinergic drug blocks all the subtype of Muscarinic receptor.

• Clonidine

• Methyldopa

• Guanfacine

• Guarabenz

What are the agonist of Pre-synaptic a₂-receptors that are hypertensives)?

Gq

This protein stimulates Phosphatidylinositol-4,5-biphosphate (PLC).

IP₃ and DAG

When Gq protein stimulates the PLC, it will release these two secondary messengers increasing intracellular calcium causing contraction.

• a₁-receptors

• M₁ and M₃-receptors

• Post-synaptic a₂-receptors

• Histamine (H₁)-receptor

• Vasopressin (V₁)-receptors

What are the five (5) examples of Gq protein?

• Epinephrine

• Norepinephrine

• Dopamine

What is an example of drug that activates a₁-receptors?

Kinase-linked Receptors

Type 3 receptor is also known as?

Enzymes

Type 3: Kinase-linked Receptors is coupled with?

Kinase

Functional group transferred phosphate.

Cell membrane

Where is Type 3: Kinase-Linked Receptors located?

Minutes - hour

What is the action of response of Type 3: Kinase-linked Receptors?

• Insulin receptors

• Platelet-derived growth factor (PDGF)

• Epidermal growth factor

These examples of Type 3: Kinase-linked Receptors controls metabolism and cell growth/differentiation.

Gene Transcription-linked Receptors or Nuclear Receptors

Type 4 receptor is also known as?

Nucleus

Where is type 4 located?

Hours-days

What is the action of response of Type 4?

Diffuse

In Type 4. the ligands need to _____ the cell to reach the receptor.

• Steroid Hormone Receptors

• Thyroid Hormone Receptors

• Vit. D and its derivatives

What are the examples of Type 4?

• Glucocorticoid (cortisol)

• Mineralocorticoid (aldosterone)

• Sex hormone

What is the examples of steroid hormone receptors?

• Affinity

• Intrinsic Activity

What are the two features of Drug-Receptor Interaction (but not all ligands stimulates)?

Affinity

The ability of the ligand to bind to receptors.

Intrinsic Activity

The ability of the ligand to activate.

IA = 1

What is the Max Quantal Affinity?

Agonist

• Has affinity with intrinsic activity

• Equal affinity, different intrinsic activity

Full Agonist: IA = 1

Classification of Ligands:

• Effect is maximal, produces all of the expected effects

• Max effect produced

Partial Agonist: IA > 0 < 1

Classification of Ligands:

• Produces some of the expected effects

• Mixed agonist and antagonist effect

• Will act as an antagonist in the presence of an agonist

• 0-1: produces some effect

Inverse Agonist: IA < 0

Classification of Ligands:

• Opposite with agonist’s pharmaceutical response

• Prevents constitutive receptor activity

Antagonist

Partial agonist in the presence of full agonist will act as an?

Morphine

This pain medication is the gold standard analgesic.

Full mu agonist

Morphine acts as?

Partial mu agonist

Nalbuphine, a pain medication, acts as?