Receptors & Cellular Transport

MechanismsJames Peerless

May 2011

Objectives Cellular Transport Mechanisms

Types Mechanisms

Receptors What are receptors for? Types

Messenger systems

Membrane Transport Mechanisms

Membrane Transport of Substances

Membranes control movement of many types of particle between intra- and extracellular compartments

Phospholipid bilayer allows diffusion of water, small molecules and lipid-soluble substances

Passive and active mechanisms

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

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

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

Primary Active Transport

Secondary Active Transport

Transport of a substance and an ion together

No direct energy input

Exo- & Endocytosis

No transport of substances through membrane

Vesicles formed by invagination of the membrane

Pinocytosis is the specialized uptake of water

Summary

Receptors

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

Role of Receptors Cell communication

Chemical messengers can be local or widespread

Regulation, mediation and amplification of signals

Allows homeostatic control

PropertiesLigands

Affinity

Competition

Activity (agonist/antagonist)

Half-life

Lipid solubility

Receptors

Specificity

Sensitivity

Saturation

Down- & Up-regulation

Signal Transduction

Membrane permeability

Membrane potential

Membrane transport

Contractile activity

Secretory activity

Protein synthesis

Clinically important

Receptor Types Ligand-gated ion channels

Acetylcholine receptors

G-protein coupled receptors Adrenergic receptors

Tyrosine kinase coupled receptors Insulin

Intracellular receptors Steroids

Ligand-gated Ion Channels

The Ach Receptor Pentameric,

transmembrane structure

2 α and β, γ, δ subunits

Ion channel opens when 2x Ach binds to α-subunits

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

Key G-protein Subunits

Subunit Acts on Second Messenger

Example

Gs Adenyl cyclase

Increases cAMP

β-adrenergic receptors

Gi Adenyl cyclase

Decreases cAMP

Opioid receptors

Gq Phospholipase C

DAG & IP3 α-adrenergic receptors

Tyrosine Kinase Coupled

Receptors

Intracellular Receptors

Questions

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

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

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