How Drugs Act 2

Question 1

What are the different GPCR subtypes?

Answer 1

• rhodopsin family
• secretin/glucagon receptor family
• metabotropic glutamate receptor/calcium sensor family

Question 2

Describe the rhodopsin GPCR family.

Answer 2

Receptors: The largest group. Receptors for most amine neurotransmitters, many neuropeptides, purines, prostanoids, cannabinoids, etc.
Structural Features: Short extracellular (N terminal) tail. Ligand binds to transmembrane helices (amines) or to extracellular loops (peptides).

Question 3

Describe the secretin/glucagon receptor GPCR family.

Answer 3

Receptors: Receptors for peptide hormones, including secretin, glucagon and calcitonin.
Structural Features: Intermediate extracellular tail incorporating ligand-binding domain.

Question 4

Describe the metabotropic glutamate receptor/calcium sensor GPCR family.

Answer 4

Receptors: Small group. Metabotropic glutamate receptors, GABA_B receptors, Ca 2+ sensing receptors.
Structural Features: Long extracellular tail incorporating ligand-binding domain.

Question 5

What is receptor desensitisation?

Answer 5

decreased responsiveness that occurs with repeated or chronic exposure to agonist

Question 6

Explain the concept of tachyphylaxis.

Answer 6

Desensitization that occurs very rapidly, sometimes with the initial dose.

Question 7

Outline the concept of tolerance.

Answer 7

Body adaptation to repeated or continuous presence of a drug. Larger doses are required to produce the original effect.

Question 8

Explain how kinase-linked receptors work.

Answer 8

1. Receptors for growth factors incorporate tyrosine kinase.
2. Cytokine receptors activate cytosolic kinases.
3. Receptors have a large extracellular ligand-binding domain connected via a single membrane-spanning helix to the intracellular domain.
4. Signal transduction involves dimerisation of receptors, followed by autophosphorylation of tyrosine residues.
5. The phosphotyrosine residues act as acceptors for the SH2 domains of a variety of intracellular proteins, thereby allowing control of many cell functions.
6. Involved mainly in events controlling cell growth and differentiation, and act indirectly by regulating gene transcription.

Question 9

What are the 2 main categories of receptors that sense lipid and hormonal signals and modulate gene transcription?

Answer 9

Cytoplasmic and nuclear.
(A third subgroup transduce mainly endocrine signals but function as heterodimers with retinoid x receptor, such as the thyroid hormone)

Question 10

Describe cytoplasmic receptors.

Answer 10

Form homodimers in the presence of their partner and migrate to the nucleus.
Their ligands are mainly endocrine in nature (eg. steroid hormones).

Question 11

Describe nuclear receptors.

Answer 11

Form heterodimers with the retinoid x receptor.
Their ligands are usually lipids (eg. fatty acids).

Question 12

Describe physical and psychological dependence.

Answer 12

Physical: Appearance of objective signs when drug is withdrawn.
Psychological: Strong desire to experience the effects of the drug repeatedly.