| What are the major types of drug receptors? | Receptors of drugs are signal transducers, there are 6 types, transmembrane ion channels, G-protein coupled receptors, transmembrane receptors with enzymatic cytosolic domain, intracellular receptors, extracellular enzymes and cell surface adhesion receptors. |
| Talk about transmembrane ion channels. | They are pore-forming membrane proteins present on the membranes, they have ion selectivity, conductance (opening duration) and mechanisms of activation or inactivation (gating or regulation)
They are two types, ligand gated and voltage gated. |
| Talk about ligand-gated ion channels. | Contains a ligand-binding site regulating the pore where ions can flow, so when receptor is activated by agonist the channel opens, they have various functions including neurotransmission, cardiac contraction...
Nicotinic receptors of acetylcholine result in sodium influx and potassium outflux generating a membrane potential causing contraction. |
| What is the effect of benzodiazepines on GABA receptors? | GABA bind on Cl- ligand-mediated ion channels, this binding is further enhanced by binding of benzodiazepines to a specific site of the channel in a subunit and gamma2 subunit, this causes increased Cl- influx and thus more hyperpolarization |
| Talk about voltage-gated Na+ channel. | When sufficient positive charge is found, Na+ channels open up allowing Na+ influx.
Local anesthetics inhibit this action for pain receptors thus not allowing the opening of Na+ voltage-gated channels.
Ex: Lignocaine |
| List some drugs acting on G-protein coupled receptors. | many therapeutic agents act on it blocking and stimulating.
Ex: adrenergic receptor agonists (asthma) and antagonists (HTN), histamine antagonists (allergies), opioid receptor agonists (analegesics), dopamine receptor antagonists (antipsychotics), serotonin receptor agonist for migrane |
| How is the structure of GPCR? | A single polypeptide chain, 7 transmembrane domains and 3 extracellular and 3 cytoplasmic loops
amino terminus outside cell and C terminus is cytoplasmic
They recruit and regulate activity of heterotrimeric G-protein (a,b,g subunits) |
| What are the characteristics of G-protein? | Trimeric protein (abg, a can dissociate from bg)
a binds GDP, associated with membrane, target membrane enzymes, activated when a subunit goes alone and dissociation expresses GTPase activity |
| Talk about the activation of GPCR. | ligand activates the receptor, which then binds g protein and stimulates release of GDP and exchange it with GTP, so activated GTP-bound a subunit dissociates from bg complex which then carries the signal to intracellular target which can be an enzyme or an ion channel.
Activation is terminated by GTP hydrolysis into GDP where a reassociates with bg.
some of them produce second messengers (cAMP activating PKA, PLC (phospholipase C) activates DAG (activate PKC) and IP3 (release Ca2+ from ER)) |
| Describe epinephrin action on GPCR. | It can increase or decrease cAMP depending on type of receptor it binds (b Gs adrenergic or a2 Gi adrenergic)
Could bind Gs (stimulate), Gi (inhibit) or Gq (coupled to PLC) protein |
