Cell Signalling Matters - Lecture Notes

Why Cell Signalling Matters. Stuart Cruickshank  “No cell is an island” Cells communicate with each other – Yeast – Multicellular organisms: growth, differentiation,and metabolism Cells send and receive information (signals) – Signaling molecules (e.g. neurotr...

Why Cell Signalling Matters. Stuart Cruickshank  “No cell is an island” Cells communicate with each other – Yeast – Multicellular organisms: growth, differentiation,and metabolism Cells send and receive information (signals) – Signaling molecules (e.g. neurotransmitters) – Receptors (GPCR ) Information is relayed within cell to produce a response (signal transduction)  Signaling molecules Released by signaling cells and produce a specific response in target cells, which have receptors for the signaling molecule Include: Hormones Pheromones Neurotransmitters Growth factors Signaling Pathways can be complex  RECEPTOR S & DISEASE Any change in the structure of ligand or ligand-binding site will result in loss of function. Intracellular receptor sites are specific. If there is an amino acid change and there is loss or change in amino acid sequence, then there is the potential for amplification, reduction or loss of signal transduction. What is a receptor?  What is a Drug? A chemical substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. A substance other than food intended to affect the structure or function of the body. Drugs  How do drugs work? Drugs produce their biological response via specific sites and mechanisms of action. Drugs may be classified as agonists or antagonists depending on the biological response. Asthma Drug Treatment of Asthma OH H CH3 N HO CH3 H3C HO Salbutamol β-adrenoceptor agonist Drugs Blocking Ion Channels Drugs Blocking Ca2+ Channels H H3C N CH3 Ca2+ CH3O OCH 3 X C C O H O NO2 Nifedipine Ca2+ Channel blocker Hypertension Drugs Blocking Na+ Channels CH3 O C2H5 NH C CH2 N C2H5 CH3 Lignocaine Na+ Channel blocker Local Anaesthetic  EFFECT OF DRUG Affinity - ability to bind to specific receptor Efficacy -ability to modify activity of cell Specificity - range of receptors for which drug has affinity Drugs Inhibiting Enzymes Angiotensin Converting Enzyme Inhibitor Angiotensin I ACE X Inhibitor Angiotensin II Vasoconstriction Captopril Hypertension  THERAPEUTICS Use of drugs in the treatment of disease DRUG THERAPY Efficacy Safety  Drugs which block Nicotinic Receptors are used as Muscle Relaxants during Surgical Procedures Atracurium O O H3CO OCH3 CH2CH2CO(CH2)5OCCH2CH2 O + + N N H3CO H3C O S O CH3 OCH3 2 H3CO OCH3 OCH3 OCH3 Ulcer  Drug Treatment of an Ulcer Histamine CH3 HN H2 S S C C CH3 C C N N H2 H2 H H Cimetidine H+ H + Histamine antagonist H+ Stomach Channels allow Ions to flow into or out of the cell Ca2+ is an Extremely Important Cellular Messenger Contraction of muscle Release of transmitter from nerve Secretion of hormones Fertilisation Ca2+ Regulation in Cells - + - + - + Drugs Blocking Ion Channels Drugs Blocking Na+ Channels OH HO O H HH O OH + N H H2N N CH2 H HO H H H OH Tetrodotoxin Na+ Channel blocker Drugs Opening Ion Channels  Drugs Opening K+ Channels Vasodilation Vasoconstriction K+ K+ open K+ channels close K+ channels K+ K+ K+ arteriole Nicorandil K+ Channel opener Vasodilatation Drugs Inhibiting Enzymes Viagra cyclicGMP Noncyclic X GMP Smooth muscle relaxation Erection Erectile Dysfunction  Drugs Inhibiting Enzymes Digitoxin Na+ 12 mM Na+ 145 mM K+ 155 mM K+ 4 mM ATP X 3 Na+ Increase Force of Cardiac 2K + Contraction ADP Congestive Heart Failure