Receptor terminology

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Receptor terminology
Protein-ligand properties specificity,
saturation, affinity, competition Antagonist
binds to receptor site and inhibits Agonist
binds to receptor site and stimulates Down-regulat
ion ? levels of messenger ?? receptors Up-regulat
ion ? levels of messenger ?? receptors Supersensi
tivity cell response to up regulation
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Receptor types
A. Intracellular receptors (steroid, thyroid
hormones) B. Cell membrane receptors i. ion
selective channels (acetyl choline) ii. receptor
has enzyme activity (insulin) iii. receptors
acting via G proteins a. adenylate cyclase (?
adrenergic, glucagon, TSH, etc.) b.
phospholipase C (? adrenergic, angiotensin II,
etc.) (b. G proteins directly on ion selective
channels-ignore)
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A. Intracellular receptors
Examples thyroid hormones (T3 T4),
steroids (estrogen, progesterone,
testosterone, aldosterone, cortisol)
fig 5-4
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B i. Ion selective channels
e.g. acetyl choline (nicotinic), many CNS
neurotransmitters (glutamate, glycine, GABA)
fig 5-5a
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B ii. Receptor has enzyme activity
fig 5-5b
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B ii. Receptor has enzyme activity (notes)
Heterogeneous group of receptors Examples
insulin (tyrosine kinase, phosphorylates itself
other proteins) growth hormone other growth
factors (JAK kinases) atrial natriuretic peptide
(guanylate cyclase),
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B iii. acting via G protein, general mechanism
fig 5-5d
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B iii. Why are they called G proteins?
Notes ? subunit has GTPase activity ?
reassembly of ???-GDP G proteins transmit
signals from gt1000 receptors
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B iiia. Adenylate cyclase cyclic AMP
fig 5-6
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Adenylate cyclase cyclic AMP (notes)
Examples where G protein is Gs (G stimulating)
?1 adrenergic receptors, glucagon, antidiuretic
hormone in kidney (V2 receptor), oxytocin,
thyroid stimulating hormone (TSH),
adrenocorticotropic hormone (ACTH), luteinizing
hormone (LH), follicle stimulating hormone (FSH),
parathyroid hormone (PTH), histamine,
cholecystokinin (CCK), corticotrophin releasing
hormone (CRH) where G protein is Gi (G
inhibiting) ?2 adrenergic receptors cAMP
dependent protein kinase protein kinase
A phosphorylates serine or threonine residues
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Cyclic AMP synthesis degradation
fig 5-7
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Amplification of cAMP effect
fig 5-8
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Protean effects of cyclic AMP
fig 5-9
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B iiib. Phospholipase C
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B iiib. Phospholipase C action
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Phospholipase C (notes)
Examples ? adrenergic, gastrin, angiotensin
II, antidiuretic hormone (ADH) on smooth muscle
(V1 receptor), thyrotropin releasing hormone
(TRH), gonadotropin releasing hormone (GnRH) G
protein is Gq DAG dependent protein kinase
protein kinase C Ca also activates protein
kinase C
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Calcium as a second messenger
extracellular Ca 1.2 mM cytosolic Ca
10-4 mM (0.0001 mM) Entry of Ca into
cytosol via voltage-gated ion channels via
ligand-gated ion channels via intracellular Ca
gated channels (heart muscle) via covalently
modified (phosphorylated) ion channels from
endoplasmic reticulum after IP3 action
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Calcium as a second messenger
Ca actions directly on protein kinase
C indirectly after binding to calmodulin ?
CM-4Ca
fig 5-11 modified
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Ca-calmodulin dependent kinases
Examples myosin light chain kinase (see smooth
muscle contraction) phosphorylase kinase (?
phosphorylase ? glycogenolysis) neurotransmitter
release synaptic transmission Protein kinases
summary protein kinase A (cAMP dependent)
ser/threo protein kinase C (DAG and Ca
dependent) ser/threo Ca-calmodulin
stimulated ser/threo various membrane bound
tyrosine kinases
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Some actions of calcium (when free in cytosol)
release of neurotransmitters by
exocytosis release of peptide and catecholamine
hormones contraction of smooth, cardiac and
skeletal muscle