Exam 2 (Lecture 14)

Nuclear Receptors Receptor Tyrosine Kinases (RTK) Cytokine Receptors Ligand-gated Ion Channel receptors G protein-coupled Receptors (GPCR)

2 Interconvertible confirmations Active vs Inactive Ligand doesn’t induce confirmation change, it locks its confirmation.

Ligands tend to be lipophilic Regulate expression of specific genes Participate in control of development, homeostasis and metabolism Can directly bind DNA; classified as transcription factors Receptors reside in either the cytoplasm or nucleus, in a complex with chaperone proteins (e.g., HSP90), and upon binding agonist the chaperones dissociate and receptors DIMERIZE either with themselves (homodimers) or another nuclear receptor (heterodimers). Receptor dimers bind to specific sites on DNA (promoter regions) designated as HREs with palindromic sequences (e.g. ATTCGGCTTA) which bind dimeric receptors and facilitate binding of other transcription factors

Hormone-responsive elements

Estrogen Androgen Glucocorticoid (cortisol) Mineralcorticoid (aldosterone) Vitamind D

Enzalutamide - prostate cancer Tamoxifen - breast cancer Lipaglyn - type II diabetes Cortisone - anti-itch and pain relief

controls metabolism and decrease inflammation used to treat allergies, asthma, autoimmune diseases, sepsis; lymphomas and leukemias

Pain and neuronal disease

Gene therapy for Parkinson’s disease

antibody that neutralizes TNF alpha and treats Crohn’s disease

fusion protein that works as TNF alpha inhibitor and treats arthritis

binds to sites called GAS (Gamma-activated-sites) in the promoter region of cytokine inducible genes and activates transcription nuclear phosphatases can inactivate

acetylcholine, serotonin, GABA, glutamate

5-HT, nicotinic acetylcholine

GABAA, Glycine

AMPA, Kainate, NMDA

3 subunits

positive allosteric modulators, enhance effect of GABA at GABAa receptor

Same effects as benzodiazepine but more toxic so been replaced

GTPi, GTPq,GTPs, GTP12

Inhibition of cAMP production, ion channels, phosphodiesterase, phospholipases

increase IP3 -> increase CA2+ Increase DAG -> increase Protein Kinase C

increase in cAMP concentration

RhoGEF -> RhoA -> ROCK