Lecture 6 - Receptors and Transporters as Drug Targets Flashcards
What are beta-adrenergic receptors activated by?
Catecholamines
Synthetic ligands developed to treat asthma, hypertension or cardiac disease
What are two catecholamines?
adrenaline and noradrenaline
What confers salbutamol’s selectivity for the beta2 adrenergic receptor?
N-trimethyl group
Explain the activity of a GPCR (4)
- Agonist binds to a receptor which induces change in receptor association alpha subunit
- GDP is released and replaced with GTP in the alpha subunit
- The alpha and betagamma subunits dissociate
- The subunits modulate activity of other enzymes or ion channels
What does agonist binding induce in the binding pocket?
A 1 angstrom contraction of the binding pocket relative to the antagonist bound receptor
What do full agonists form hydrogen bonds wiht?
Two conserved serine residues in transmembrane helix 5
What do partial agonists interact with only?
Serine211
What is the difference between a passive transporter and an active transporter?
Active transporters require energy and move substrates against a concentration gradient
What do primary active transporters use for energy? (2)
Light, ATP hydrolysis
What do secondary active transporters use for energy?
Pre-existing ion gradients
What are two main families of neurotransmitter transporters on the pre and post synaptic neurones?
- Glutamate transporter family
- Neurotransmitter sodium symporter (NSS) family
What are some substrates for the NSS family? (5)
GABA, glycine, dopamine, noradrenaline, serotonin
What are all neurotransmitter transporters?
Secondary active transporters
What are the substrate of the glutamate transporter family? (2)
Glutamate and aspartate
What chemical gradient is the NET transporter coupled to?
Na+ and Cl-
