G protein coupled receptors and second messengers

Question 1

Sympathetic nervous system

Answer 1

All the physiological effects of activation of the sympathetic nervous system are brought about by the action of transmitter substances on specific cell membrane receptors (adrenoceptors) that convey the message from the outside to the inside of the cell

Sympathetic nerves release noradrenaline

Adrenal medullae release adrenaline and noradrenaline

2 main subtypes of receptor to which catecholamines bind
- alpha adrenoceptors
- beta adrenoceptors

These two groups can be further subdivided

Question 2

Adrenergic receptors: Agonist potency order

Answer 2

Agonist potency order has now been determined for all 5 main types of adrenoceptor

alpha1 noradrenaline ≥ adrenaline&raquo_space; isoprenaline

alpha2 adrenaline > noradrenaline&raquo_space; isoprenaline

beta1 isoprenaline > noradrenaline > adrenaline

beta2 isoprenaline > adrenaline > noradrenaline

beta3 isoprenaline > noradrenaline = adrenaline

Question 3

Structure of adrenoceptors

Answer 3

All adrenergic receptors are part of the family of G protein-coupled receptors (metabotropic receptors)

Recruit intracellular proteins, known as G proteins, in order to produce their cellular effects

Integral membrane protein

Single polypeptide chain: 400 - 500 amino acids

Extracellular N-terminus, intracellular C-terminus

7 transmembrane alpha helices

Binding site buried within a cleft between the  helices
(i.e. within the plane of the membrane)

Question 4

G protein coupled receptors

Answer 4

alpha and beta -adrenoceptors recruit different intracellular G-proteins

Hence, alpha and beta adrenoceptors utilise different intracellular messaging systems to produce their cellular effects

Site-directed mutagenesis experiments have shown that the long third cytoplasmic loop is the region of the receptor that couples to the G protein (although the C-terminus may also be involved)

Differences in the amino acid sequence of the long third cytoplasmic loop are the basis by which alpha and beta adrenoceptors interact with different G proteins, and produce different cellular effects

Question 6

Sympathetic nervous system

Answer 6

All the physiological effects of activation of the sympathetic nervous system are brought about by the action of transmitter substances on specific cell membrane receptors (adrenoceptors) that convey the message from the outside to the inside of the cell

Sympathetic nerves release noradrenaline

Adrenal medullae release adrenaline and noradrenaline

2 main subtypes of receptor to which catecholamines bind
- alpha adrenoceptors
- beta adrenoceptors

These two groups can be further subdivided