L4 receptors.pdf
Transcript
L4 Receptors Define a (pharmacological) receptor Identify the main cellular locations of receptors Identify the 4 functional types of receptor Describe how these functional types provide a wide range of cellular signalling Give specific examples of each functional type Define a (pharmacological) rec...
L4 Receptors Define a (pharmacological) receptor Identify the main cellular locations of receptors Identify the 4 functional types of receptor Describe how these functional types provide a wide range of cellular signalling Give specific examples of each functional type Define a (pharmacological) receptor In pharmacology, receptors are binding sites or drug/toxin targets that respond to neurotransmitters and neurohormones Identify the main cellular locations of receptors Nuclear receptors Interact with DNA e.g. steroid receptors Regulate gene expression and protein synthesis Often found in cytosol and transported to nucleus when needed Can be identified with zinc finger structures Intracellular receptors E.g. ryanodine receptors and inositol triphosphate receptor Effectors for intracellular signalling pathways e.g. increasing calcium concentration Commonly found in the sarcoplasmic reticulum and endoplasmic reticulum. Ryanodine receptor is activated by calcium – calcium induced calcium release IP3 receptor activated by inositol triphosphate. Both of above ligand gated ion channels – let calcium out Plasma membrane receptors Ligand gated ion channels – ionotropic, receptor operated channels G protein coupled receptors – metabotropic, seven TMD receptors Intrinsic enzyme receptors -pleiotropic (more than one effect), receptor tyrosine kinases – receptor is an enzyme Responds to neurotransmitters and neurohormones Can activate second messengers Identify the 4 functional types of receptor. Describe how these functional types provide a wide range of cellular signalling. Give specific examples of each functional type Ligand Gated Ion Channels Three types: o Nicotinic R like, nAChR, 5-HT3, GABA-A, Glycine, ZAC o ATP R – P2X o Inotropic glutamate R – NMDA, AMPA, Kainate Structure: All have an extracellular ligand binding site and have a pore for ions to pass through. Function: Can be excitatory or inhibitory depending on whether cations or anions pass through the pore. G-Protein Coupled Receptors Many types: o Rhodopsin like – (hundreds) e.g. mACh, opioid, noradrenaline, cannabinoid, dopamine, ATP, NPY, all 5-HT except 5-HT3, etc. o Metabotropic Glutamate Receptor like – GABA-B, mGluRs(1..8) o Secretin Receptor like- Vasointestinal polypeptide, Parathyroid hormone Structure: o Rhodopsin like = 7 transmembrane domains o mGluR-like (metabotropic glutamate like) = often work as dimers with clamshell/venus fly trap-like extracellular domain with ligand and allosteric binding site. Function: To activate second messengers to have inhibitory or excitatory effects Intrinsic Enzyme Receptor Families Two types: o Receptor tyrosine kinases (phosphorylates tyrosine kinase residues – insulin receptor and nerve growth factor receptor (TrkA) o Receptor guanylate cyclase – atrial natriuretic peptide (ANP) receptor. Structure: Function: o Exist as monomers then dimerise to form functional unit o Stages: Ligand binding, dimerization, autophosphorylation, substrate phosphorylation Sort sequence is unique to receptor subtype.
