M&R Session 6 (Lecture 6.1) Flashcards
Describe paracrine signalling.
1) Local mediator released into interstitium
2) Binds to receptors on cells within the local vicinity to cause effects
Describe endocrine signalling.
1) Hormone released into bloodstream to act on distant cells
What is a receptor?
Molecule that recognises a second molecule (ligand) or family of molecules and which in response to ligand binding brings about regulation of a cellular process.
If a receptor is unbound, what is its state?
Functionally silent
What is a ligand?
Any molecule that binds specifically to a receptor site.
What is an agonist?
A ligand that may produce activation of a receptor
What is an antagonist?
A ligand that combines with a receptor site without causing activation. Competitively competes with agonist thus not allowing agonist binding
Compared to an enzyme, what is the affinity of a receptor for its ligand?
Higher usually nano or micro molar.
How are receptors classified and sub-classified?
Classified according to:
Specific physiological signalling molecule (agonist) recognised
Sub-classified:
Affinity (tightness of binding) of a series of antagonists
Give an example of an antagonist for the M1, M2 and M3 receptor subtypes?
M1 - Pirenzipine
M2 - Gallamine
M3 - Hexahydrosiladiphenol
What is the difference between a receptor and acceptor?
Receptor:
Silent at rest
Agonist binding stimulates a biological response
Acceptor:
Operate in absence of ligand
Ligand binding alone produces no response
Give an example of an acceptor?
Dihydrofolate reductase
What are the four types of signal transduction ?
1) Membrane-bound receptors with integral ion channels
2) Membrane-bound receptors with integral enzyme activity
3) Membrane - bound receptors which couple to effectors through transducing proteins
4) Intracellular receptors
Give examples of mem-bound Rs with integral ion channels.
nAChR GABA R Glycine R NMDA, AMPA and kainate IP3 R
Give examples of classical and non-classical ligand gated ion channels?
Classical : nAChR
Non-classical : ATP sens K+ channel, P2x purinoceptor, Ryanodine receptor
Give an example and describe a mem-bound Rs with integral enzyme activity?
Two alpha helices come together (dimerise) to form functional receptor with cytoplasmic catalytic domain
e.g. PDGFR
Atrial natriuretic peptide (ANP) receptor - linked directly to guanylyl cyclase (GTP»_space;> cGMP)
Growth receptors (insulin, EGF, PDGF) - linked to TK
Describe the process of signalling via TK-linked receptors.
1) Binding with agonist to receptor
2) Dimerisation and autophosphorylation on cytoplasmic tail by TK towards tyrosine residues
3) EITHER enzyme detects Y-P and binds to it causing the enzyme to be activated e.g. SH2 (src - homology 2 domains)
OR
3) Y-P detected by transducer e.g. domain transducers e.g. IRS-1, Grb2 which gets itself Y-P and activates enzymes
Describe mem-bound Rs that signal through transducing proteins / 7TMD Rs? Give examples.
1) Coupled through G-proteins to enzymes or channels with ligands generally binding into cleft
Examples:
Adrenaline binding to Beta-adrenoceptors activates the enzyme adenylyl cyclase via G-protein Gs
Acetylcholine binding to M2 muscarinic acetylcholine receptors stimulates K+ channel opening via a different G-protein, Gi (inhibits cAMP prodn)
Describe the intracellular receptor family.
1) Inhibitory protein complex blocks RNA pol from transcribing the steroid sens genes.
2) Once steroid binds to its binding site, this causes dissociation of the inhibitory complex so the DNA binding site is exposed allowing transcription,
What are partial agonists?
Agonists which stimulate a receptor but are unable to elicit the maximum cell response.
