Receptors Flashcards
Pharmacology II
What are the three most important steps between drugs and receptors?
1st step - drug-receptor interaction
2nd step - chemical communication
3rd step - pharmacological effect
What does mean chemical communication?
Chemical communication is responsible for growth, development, proliferation, differentiation, tissue and organ formation, maintenance and physiological regulation. Communication can be direct or indirect, and it determines how well a cell gives or receives messages. Receptors have two domains: 1. binding domain and 2. effector domain. If receptors are too far away then we have receptor coupling.
What are receptors?
Receptors are components of cells or tissue that when bound to a drug/molecule produce a chain of chemical reactions that lead to drug’s observed effect. They are important for three things: reception, signal transduction, and response. They differ in the intracellular response they produce.
What is another name for ligand-gated channels and what types of ion channels do we have?
Ligand-gated receptors are also known as ionotropic receptors which are very fat neurotransmitters. Ion changes differ in stimuli by which they are activated. We have three types, including:
1. voltage-gated (membrane potential)
2. ligand-gated (neurotransmitter)
3. mechanically-gated (p, T, touch)
Explain the types of voltage-gated ion channels.
- Ca2+, they are responsible for 2n message production. They are involved in:
a. secretion of hormones
b. contraction of muscles
c. activation of protein kinase
d. initiation of signal transduction
e. regulating gene expression - Na+ and K+, stimulate neurons and skeletal muscles.
- Cl-, regulates pH, volume homeostasis, cell division, differentiation, and proliferation.
What are the three superfamilies of ligand-gated receptors?
a. cys-loop (5)
b. glutamate (4)
c. purinoreceptors (3)
Characteristics of ligand-gated receptors.
They are fast neurotransmitters, react in ms, do not produce an intermediate response, responsible for synapses and skeletal muscles.
Nicotine-Ach receptor
Ach binds to two binding sides (alpha subunits) at ligand-gated receptors. It causes the opening of an ion channel that is lined with negatively charged amino acids. It enables Na+ ions to pass inside the cell membrane causing muscle contraction. The same happens when nicotine binds to two binding sites on the receptor. It happens on dopamine neurons causing the production of dopamine that is responsible for addiction.
GABA receptors
GABA molecules bind to two binding sites on ligand-gated receptors. Channel opens and it is lined with negatively charged amino acids. It allows Cl- to go inside the cell membrane whereas K+ ions for outside the cell membrane. It regulates brain function, anxiety, and muscle relaxation. It has an inhibitory action used for epilepsy and spasticity.
NMDAR receptors
When glutamate binds to receptors it causes an influx of Ca2+ ions that are uptaken by postsynaptic neurons in CNS. It can cause so much Ca2+ ions entry that leads to cell death.
What is another name for GPCR and what kind of structure it has?
It is known as a serpentine receptor, which consists of three subunits (alpha, beta, and gamma). The alpha subunit has GDP bound when it is inactivated.
Explain GPCR.
Signaling molecules bind the binding domain on the receptor. After that receptor undergoes active conformation. Alpha subunit becomes activated by transforming GDP into GPT. When the alpha subunit is activated it separates from the beta/gamma subunit and binds to the target protein (enzymes), by activating it produces a second message. Beta/gamma subunits can do the same, they bind also to target protein (ion channel, protein kinase) and activate it but without the production of a second message. When GTP changes to GDP, it returns to its original inactivated state.
List the types of G protein targets.
- adenyl cyclase - forms cAMP
- phospholipase C - IP3 and DAG formation
- ion channels - Ca2+ and K+
- Rho A /Rho kinase - cell growth, development, proliferation, differentiation, smooth muscle contraction
- MAP kinase - cell division
List the types of GCPR pathways.
- Galphas - cAMP (stimulator)
- Galphaq - DAG/IP3 (stimulator)
- Galphai - cAMP (inhibitor)
Explain 2nd message of IP3/DAH pathway.
Ach binds to M3 muscarinic receptors and by undergoing activation of GPCR also activates alpha/beta/gamma subunits. When the alpha subunit is activated GDP is transformed into GDP. After that alpha subunit binds to phospholipase C and the segment of phospholipid membrane PIP2 causes the formation of DAG and IP3. Further, IP3 binds to the ion channel on ER and causes the release of Ca2+ ions into the cytoplasm. Ca2+ ions bind to the calmodulin receptors forming the Ca2+-CaM complex. It further binds to MLC kinase causing contraction of smooth muscles. On the other hand, DAG binds to protein kinase C and causes phosphorylation of the target protein in order to produce cell response. It can bind to MARCKS protein which can cause a change in cell shape or a change in gene expression through transcription factors.