VOC - Molecular Pharmacology I

Question 1

How can the Anatomical Classification of substances be determined?

Answer 1

Different vessels gave distinct responses to constrict or dilate in response to noradrenaline addition

Question 2

How can the Pharmacological Classification of substances be determined?

Answer 2

Ahlquist noted a rank order of potency for adrenergic agonists depending on the nature of the response

Question 3

What is the order of potency of isoprenaline, noradrenalin and adrenalin for Contricting Responses?

Answer 3

Noradrenalin>adrenalin> isoprenaline

ALPHA RECEPTOR

Question 4

What is the order of potency of isoprenaline, noradrenalin and adrenalin for Dilating Responses?

Answer 4

Isoprenaline>adrenalin> noradrenalin

BETA RECEPTOR

Question 5

What affects the chemical response of the agonist?

Answer 5

The chemical structure of the antagonist

Question 6

How do Yohimbine, Propanolol and Pindolol affect alpha and beta receptors?

Answer 6

Yohimbine blocks alpha and has no effect on beta receptors

Propanolol blocks Beta receptors and has no effect on alpha receptors

Pindolol blocks beta receptors (less effect on beta2) and has no effect on alpha

Question 7

What does molecular classification through gene cloning involve? (4)

Answer 7

1. Identify and sequence the cDNA for the receptor
2. Predicts the amino acid sequence of the receptor
3. Repeat for all receptor sub-types and compare amino acids to give a molecular classification.

Often, it leads to the identification of distinct subtypes not realised by pharmacological classification

Question 8

What are the methods used to reveal the molecular basis of receptor sub-types? (4)

Answer 8

Protein Purification and cDNA Cloning

• 1980
• Purify protein sequence and screen cDNA libraries

Receptors cloned and identified: 1 or 2

Homology Cloning

• 1980-1990
• Low stringency

Receptors cloned and identified: 10 or 20

Expressed Sequence Tags (EST)

• 1990
• Assembling random sequences into contiguous

Receptors cloned and identified: 100

Genome Data Mining

• 1990-
• Extraction of homologies and shared relationships from sequenced genomes

Receptors cloned and identified: 1000

Question 9

How is post-genomic receptor family building accomplished?

Answer 9

cDNA sequences →

Predict protein sequences →

Sequence comparison, established function and protein prediction leads to diverse receptor being identified as relatives of one family

Question 10

What is the nomenclature for adrenoreceptors?

Answer 10

• Superfamily: G-protein coupled receptor
• Family: Rhodopsin family
• Sub-family (Class): Adreno-like receptors
• Sub-type (Sub-class): Alpha and Beta receptors