Receptors

receptor

located on/within a cell that interacts with a drug/ligand to start a response

second messenger

generated; begin another cascade

transduction/conversion

external signal→receptor→intracellular signal→cell response

ligands

receptor activation (neurotransmitters, peptides, hormones)

homodimer plasma membrane receptor

two identical subunits

heterodimer membrane receptor

two diff subunits

heteropentameric ion channels

5 diff/identical subunits

receptor subtypes

similar structure but different pathways

conformational change

ligand binding changes shape of receptor=activation

signal transduction

transmitted across membrane through transmembrane domain

amplification

single ligand-receptor activates multiple intracellular pathways

desensitization pathway

receptor responds to overstimulation→receptor removed→new pathway forms (prevents overstim)

desensitization caused by

modification of receptor by other proteins, receptor internalization, exhaustion of signaling mediators

ligand-gated ion channel (LGIC)

(milliseconds) transmembrane channel protein, selective for specific ions, changes in membrane potential (neurotransmitters)

nicotinic acetylcholine receptor nAChR

Na/K channel activated by acetylcholine (LGIC)

Gaba- A receptor

Cl channel activated by gamma-aminobutyric acid (hyperpolerization)

N-methyl-D-aspartate receptor (NMDAR)

Ca/Na channel activated by glutamate and glycine for synaptic activity

7-TMS G-protein coupled receptors

(seconds) cell surface receptors relaying signal from out to in (B1, B2, B3)

G protein activtion

alpha and beta gamma dissociate; activate separate targets

alpha subunit

swaps GDP→GTP then activates target; hydrolizes GTP→GDP to start over

Gs proteins

stimulating alpha subunit

Gi proteins

inhibitory alpha subunit

Gq proteins

activates phospholipase to inc cell Ca and kinase

Enzyme/Kinase-linked receptors

(hours) tyrosine kinase and cytokine receptors; external & internal component

tyrosine kinases (RTKs)

possess intrinsic tyrosine kinase activity; activated by growth factors

tyrosine-kinase associated receptors

no intrinsic kinase activity but recruit/activate intracellular tyrosine kinases (JAK)

receptor serine/threonine kinases

activate by phosphorylating serine or threonine residues on intercellular proteins

receptor guanylyl cyclases

catalyze cyclic GMP production (second messenger)

receptor tyrosine phosphatase

inhibit signaling by removing phosphate groups from proteins

intracellular receptors

(hours) in cytoplasm or nucleus, bind to lipid-soluble hormones for gene expression regulation

ligand- binding domain of SHRs (intracell)

recognizes and binds to hormone

DNA binding domain of SHRs

binding to hormone response elements (HREs) on DNA for gene expression regulation

transactivation domain of SHRs

activate/repress to regulate transcription