Intracellular receptors for lipid soluble agents

Ligand regulated transmembrane enzymes

Cytokine receptors

Ligand and voltage gated channels

G Proteins and Second messengers

The activated intracellular receptors stimulate transcription of genes by binding to specific RNA sequences

Ligand binding causes the receptor to bind to hsp90, a second messenger

The gene active ligand cannot alter a pathological state within minutes

Effects are transient and quickly resolve

Binding of ligand to intracellular domain ligand binding domain

Cytoplasmic enzyme domain acts as the effector element

Catalyzes phosphorylation of tyrosine residues (Y) on different target signaling proteins

Intensity & duration limited by down regulation

Examples of ligands include corticosteroids

Mechanism closely resemble intracellular receptors for lipid soluble agents

Phosphorylation of signal transducers will cause activation of transcription molecules (STAT)

STAT dimers travel to nucleus and regulate transcription

Example of ligands includes growth hormone

Natural ligands include serotonin

Receptors decrease transmembrane conductance of the relevant ion altering the electrical potential across the membrane

Transient opening of central aqueous channel allows one way ionic movement across the membrane

There is a lag period of minutes to hours before onset of action

G protein changes activity of effector element which changes concentration of second messenger

Duration of activity of effector element depends on binding of ligand rather than longevity of G-GTP complex

Noradrenaline is an example of natural ligand

Signal terminated by hydrolysis of GDP

G-mediated responses to drugs and agonists attenuate with time

Desensitization is irreversible

Increase in actual number of receptors is known as upregulation

Decreases the activity of receptors is known as downregulation

Breakdown of carbohydrates in liver by β-adrenomimetic catecholamines

Sodium excretion in the kidney by vasopressin

K+ homeostasis by parathyroid hormone

Decreased heart rate by β-adrenomimetic

cAMP regulates production of adrenal & sex steroids in response to corticotropin/FSH

IP3 inactivated via dephosphorylation

Ca2+ passively removed via diffusion

Actions of cGMP terminated by enzymatic degradation of cyclic nucleotide & dephosphorylation of kinase substrate