first messengers (ligands) and their interaction with receptors
Mar 27, 2015
first messengers (ligands) and their
interaction with receptors
I
A selectionof
firstmessengers
A selectionof
firstmessengers
Interaction ligand-receptorwell known
Ligand/receptor interactions vary greatly between small ligands, like neurotransmittors and certain
hormones, and protein ligands, like the cytokines or growth factors
Quantitative aspects of ligand/receptor interactions are well studied for small ligands, binding to ions channels or 7-TM
proteins
Interaction ligand-receptorwell known
Small ligands have a limited number of interactions with their receptor; three in the case of adrenaline (serine, serine and
aspartate)
2
1
3 2
topview
Large protein ligands have a large number of interactions with their receptor (numerous amino acides involved as indicated by
the green surfaces)
Interleukin-1Interleukin-?
Another example of multiple sites of interaction between ligand and receptor, this time in the case of TGF
binding to the EGF receptor
Characteristics of receptor binding: saturable (specific) binding sites
Linear scale Logarithmic scale
Maximum specific binding
EC50
High receptor numbers increase the sensitivity of the system. Cells often express receptors in excess
Characteristics of receptor binding: inhibition of cellular response by an antagonist
Dose responsein presence of antagonist(the presence of the antagonist preventsbinding of adrenaline)
Agonistonly
Antagonists are substances that bind to the receptor without causing a cellular response; in doing so they compete with the action of the physiological ligand.
Agonist are substances that bind to the receptor and mimic the action of the physiological ligand.
Agonists and antagonists are frequently used in pharmacological intervention of disease, for instance -adrenaline antagonists (« -blockers ») are applied to reduce the heart rate and to reduce the force of contraction (in case of a history of cardiac failure)
Relationship between cellular reponse (3), second messenger generation (2) and ligand binding (1)
(1)(2)(3)
Characteristics of receptor binding: a dynamic receptor-ligand interaction
Ligand receptor binding strategy for nerve signal transmission: low affinity acetylcholine receptors (KD 20-80 M) in a very small
volume (the synaptic cleft) with the presence of acetylcholinesterase. This warrants a rapid and, importantly,
transient response.
Rapid and transient receptor occupation, as in the case of acetylcholine at the neuromuscular junction, permits rapid and
transient muscle contraction.
Ligand receptor binding strategy for growth factor signal transduction: very high affinity receptors (KD 100 nM),
slow and long lasting responses. This allows for economization of growth factor production (large proteins
that are diluted in total body volume)..