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- Intercalating agents - Alkylating agents - Strand breaking agents
Subfamilies:
Hybrid
- class 2 receptors that form obligate heterodimers with RXR - includes: thyroid hormone receptor, vitamin D receptor
Class 2
- in nucleus (induces heterodimerization with retinoid x receptors, which causes co-repressor to dissociate, and co-activator protein to bind - include: fatty acid/cholesterol receptors, xenobiotic receptors (induces drug metabolizing enzymes-P3A)
Class 1
- in cytoplasm associated with heat shock proteins (allows class 1 receptors to dissociate from heat shock proteins and homodimerize) - receptors for steroid hormones: glucocorticoids, mineralcorticoids, oestrogen, progesterone, androgen
Characteristics: - Ligands include: hormones, vitamins, "orphan receptors" - responds in hours-days
Structure: - no transmembrane domain (2 terminal domains bound above core structure: N-terminus and C-terminus) -found in cytoplasm or nucleus of cell
Types: - Kinase-linked receptors - Receptor tyrosine kinase: Growth factor receptors (epidermal and nerve) and Toll-like receptors (bacterial infection) - Serine/Threonine Kinase: transforming growth factor receptor - signaling cascade - Kinase-associated receptor - no integral kinase - associate with cytosolic tyrosine kinase - Jak-stat signaling pathway
Characteristics: - Ligands include: growth factors, cytokines, insulin, bacterial LPS - Responds in minutes-hours
Structure: - 1 transmembrane domain: connects EC and cytoplasmic domains - form dimer pairs when activated - *have an additional integral enzymatic capacity in phospho-kinase domains
Mechanism of Activation: - ligand binds receptor to induce a conformational change - high affinity binding sites for G protein trimer are exposed - GDP bound to alpha subunit is converted to GTP when G protein complex binds GPCR - GDP -> GTP releases activated alpha subunit from beta/gamma subunit complex and receptor
Subfamilies: - Rhodopsin family - Secretin/glucagon family - Metabotropic glutamate receptor/ Ca sensor
Metabotropic glutamate
- small group - GABAb receptors
Secretin/Glucagon
- receptors for peptide hormones (calcitonin, oxytocin, renin) - intermediate EC tail with ligand binding domain
Rhodopsin
- Largest group - mainly amine neurotransmitters, neuropeptides, purines, protanoids, cannabinoids - short extracellular tail (N-terminal) - ligands bind to helices or extracellular hoops
Characteristics: - Ligands: ACh, 5HT, dopamine, opioids, etc. - GPC receptor agonists are similar to ligand gated: RAPID effects (seconds) , but not as fast as ligand gated - receptor desensitization - associate with ligand-bound receptors: anchored to cytoplasmic surface of cell membranes
Structure: - 7 transmembrane domains (alpha helices) - extracellular and cytoplasmic domain - trimeric: alpha subunit (G alpha s, G alpha i, G alpha q, G alpha 12), beta subunit, gamma subunit
Characteristics: - respond extremely rapidly (millisec) to activate and recover - controls synaptic events - no difference to speed of transfer whether drug or biological ligand binds - length of time pore remains open depends on ligand
Structure: - 4 transmembrane domains of alpha helices - Pentameric complex of subunits - Ligands: Ach, GABA, Glutamate, 5-HT3 - Selective: central aqueous pore with high concentration of negatively or positively charged amino acids to make the pore either cation-selective (nicotinic Ach) or anion-selective, respectively. - anion selective: GABAa receptor, 5-HT3
