12. Receptor and Effector Mechanisms Flashcards
What is the effect of ligand binding to ligand-gated ion channels?
It allows ions to move into or out of the cell.
What is the effect of ligand binding to receptors with intrinsic enzymatic activity?
Activates an enzyme activity that phosphorylated the receptors and other substrates.
What are agonists?
They bind to the receptor and activate it.
What are antagonists?
The bind to the receptor but do not activate it, so block the effects of agonists at the receptor.
What are examples of B-adrenoceptors agonists and antagonists?
Agonists: B2 specifically, salbutamol and salmeterol (a to-asthma).
Antagonists: propranolol and atenlol (cardiovascular).
What are some examples of u-opioid receptor agonists?
Morphine and fentanyl, analgesia/anaesthesia.
What are some examples of D2 dopamine receptor antagonists?
Haloperidol and sulpiride, anti-schizophrenics (neuroleptics).
What can the results of genetic changes to GPCRs be?
Loss of function or gain of function.
What is retinitis pigmentosa caused by?
Loss of function mutation to rhodopsin.
What is nephrogenic diabetes insipidus caused by?
Loss of function mutation to V2 vasopressin receptor.
What is familial male precocious puberty caused by?
Gain of function mutation to luteinising hormone receptor.
What can different GPCRs respond to?
Ions, neurotransmitters, peptide and non-peptide hormones, and large glycoproteins.
What is the basic, common structure of GPCRs?
Single polypeptide chain, 7-transmembrane spanning regions, extracellular N-terminal and intracellular C-terminal.
Where are the binding site on GPCRs?
Formed by 2-3 transmembrane domains in some receptors of by the N-terminal region in others (if the ligand is large).
How do GPCRs cause a change in cellular activity?
Activated GPCR must interact with a G protein. This activates the G protein and causes a change.
What is the structure of G proteins?
Made of three subunits: alpha, beta and gamma (although beta and gamma act functionally as one subunit).
How are G proteins activated?
By the binding of GPCRs that causes GTP to exchange for GDP on the G protein alpha-subunit.
How does a response happen after G protein activation?
The a-By complex dissociates and each then interacts with an effector protein.
How is a G protein signal terminated?
The a-GTYP and/or By interaction with effectors lasts until the a-subunit GTPase activity hydrolysed GTP back to GDP. Then a-GDP and By subunits reform the inactive heterotrimaric complex.
When acting on B-adrenoceptors, which G protein does the ligand adrenaline/noradrenaline act on? And what is the effect on the effector?
Gsa and it has a positive, stimulatory effect on the effector adenylyl cyclase.
When acting on a2-adrenoceptors, which G protein does the ligand adrenaline/noradrenaline act on? And what is the effect on the effector?
Gia, it has a negative, inhibitory effect on the effector adenylyl cyclase.
When acting on a1-adrenoceptors, which G protein does the ligand adrenaline/noradrenaline act on? And what is the effect on the effector?
Gqa, has a positive, stimulatory effect on the effector phospholipase C.
When acting on rhodopsin, which G protein does the ligand light act on? And what is the effect on the effector?
Gta (transducin) has a positive, stimulatory effect on the effector cyclic GMP phosphodiesterase.
When acting on M2/M4-muscarinic receptors, which G protein does the ligand acetylcholine act on? And what is the effect on the effector?
Gia, inhibitory effect on adenylyl cyclase.
When acting on M1/M3-muscarinic receptors, which G protein does the ligand acetylcholine act on? And what is the effect on the effector?
Gqa, positive, stimulatory effect on the effector phospholipase C.
What do the toxins cholera toxin and pertussis toxin cause?
CTx -> cholera.
PTx -> whooping cough.
How does the cholera toxin interfere with G protein function?
It eliminates GTPase activity of Gsa so it is irreversibly activated.
How does the pertussis toxin interfere with G protein function?
It interferes with GDP/GTP exchange on Gia so it is irreversibly inactivated.
What are the three super families of cell-surface receptors?
Ligand-gated ion channels, receptors with intrinsic enzymatic activity and G protein-coupled receptors.
