Cell Membrane Receptor Signalling

A receptor is a protein, often integral to a membrane, containing a region to which a ligand (chemical messenger) binds specifically to elicit a response.

They may be grouped into three classes based on mechanism of action:

1. Altered ion permeability (ion channels / ionotropic receptors)

Membrane spanning complexes with the potential to form a channel through the membrane.
There are three families:

• Pentameric → contain 5 membrane spanning units (eg, nicotinic Ach receptor at the NMJ which allows a Na channel to form, GABA A receptor which allows a Cl channel to form, 5HT3 receptor)
• Ionotropic glutamate → NMDA, AMPA and kainate ionotropic ligand gated ion channels. They form Na, K and (NMDA only) Ca channels when glutamate binds
• Purinergic receptors → PX1 and PX2 are activated by ATP, permeable to Na, K and Ca, and are associated with mechanosensation and pain.

2. Production of intermediate messengers (Metabotropic receptors)

Membrane bound systems that transduce a ligand gated signal presented on one side of the cell membrane into an intracellular signal transmitted by intermediate messengers.
These messengers may be:

• G proteins (most common) → binding of a chemical messenger to a G-protein coupled receptor activates the G protein, which in turn amplifies and transmits the signal to the appropriate target molecules. This can be done in several ways:
  • Activation of phosplipase C (Gq), with intracellular production of DAG, IP3 and other inositol phosphates (eg; angiotensin II, noradrenaline on alpha 1 receptors, vasopressin on V1 receptors)
  • Activation (Gs) or inhibition (Gi) of adenylyl cyclase, causing increased or decreased levels of intracellular cAMP (eg, noradrenaline increases cAMP via beta1 receptors, noradrenaline decreases cAMP via alpha 2 receptors)
  • Increase in cGMP (eg, atrial natriuretic peptide, nitric oxide)
• Tyrosine kinase → eg, insulin activates tyrosine kinase resulting in the phosphorylation of various proteins
• Guanylyl cyclase → eg, NO, atrial natriuretic peptide

3. Regulation of gene transcription (Nuclear receptors)

• Steroids and thyroid hormones act through intracellular receptors to alter the expression of DNA and RNA, and indirectly alter the production of intracellular proteins.

JC 2019

Answer by JC