Receptors & Cellular Transport Mechanisms

1. Receptors & Cellular Transport Mechanisms James Peerless May 2011

2. Objectives • Cellular Transport Mechanisms • Types • Mechanisms • Receptors • What are receptors for? • Types • Messenger systems

3. Membrane Transport Mechanisms

4. Membrane Transport of Substances • Membranes control movement of many types of particle between intra- and extracellular compartments • Phospholipidbilayer allows diffusion of water, small molecules and lipid-soluble substances • Passive and active mechanisms

5. Simple Diffusion • Random movement of molecules • Passive process • Net movement occurs down a concentration gradient • kp dependent upon: • Temperature, membrane permeability • molecular properties (lipophilicity, charge, MW) Q = kpA(C1-C2)/T

6. Facilitated Diffusion • Molecule moves down concentration gradient • Rate determined by carrier and solute concentration • Rate of transport is ‘facilitated’ by a carrier molecule • Carrier • Channel

7. Active Transport • Specialized facilitated diffusion • Mediated by membrane carrier proteins & requires energy • Transport of substances against their concentration gradient • Affecting transport: • Carrier saturation and density of carriers • Speed of carrier conformational change

8. Primary Active Transport

9. Secondary Active Transport • Transport of a substance and an ion together • No direct energy input

10. Exo- & Endocytosis • No transport of substances through membrane • Vesicles formed by invagination of the membrane • Pinocytosis is the specialized uptake of water

11. Summary

12. Receptors

13. Receptors “A molecule that recognises specifically a second molecule whose binding brings about the regulation of a cellular process.” Lambert DG (2004). Drugs & Receptors. Continuing Education in Anaesthesia, Critical Care & Pain; 4 (6): 181-4

14. Role of Receptors • Cell communication • Chemical messengers can be local or widespread • Regulation, mediation and amplification of signals • Allows homeostatic control

15. Properties Ligands Receptors Specificity Sensitivity Saturation Down- & Up-regulation • Affinity • Competition • Activity (agonist/antagonist) • Half-life • Lipid solubility

16. Signal Transduction • Membrane permeability • Membrane potential • Membrane transport • Contractile activity • Secretory activity • Protein synthesis

17. Clinically important Receptor Types • Ligand-gated ion channels • Acetylcholine receptors • G-protein coupled receptors • Adrenergic receptors • Tyrosine kinase coupled receptors • Insulin • Intracellular receptors • Steroids

18. Ligand-gated Ion Channels

19. The Ach Receptor • Pentameric, transmembrane structure • 2 α and β, γ, δ subunits • Ion channel opens when 2x Ach binds to α-subunits

20. G-protein Coupled Receptors • Extensive and important • Adrenergic • Muscarinic • Opioid • Act via second messengers • cAMP increased or decreased • Activation of protein kinases • Protein phosphorylation • Inactivated by phosphodiestereases

22. Key G-protein Subunits

23. Tyrosine Kinase Coupled Receptors

24. Intracellular Receptors

25. Questions

26. MCQ 1 • The rate of diffusion of a gas (Fick’s Law) across a membrane: (a) is directly proportional to the area (b) is directly proportional to the partial pressure gradient (c) is inversely proportional to thickness of the membrane (d) is directly proportional to the molecular weight (e) is inversely proportional to the density of the gas T T T F F

27. MCQ 2 The following receptors are part of a ligand-gated ion channel: • A) opioid mu receptor • B) muscarinic cholinergic receptors • C) nicotinic cholinergic receptors • D) GABAA receptors • E) GABAB receptors F F T T F

28. Summary • Cells have passive and active mechanisms for controlling passage of molecules across boundaries • Intercellular communication allows homeostatic control via the specific use of chemical messengers and cellular receptors