Receptor terminology
Protein-ligand properties: specificity, saturation, affinity,
competition
Antagonist: binds to receptor site and inhibits
Agonist: binds to receptor site and stimulates
Down-regulation:  levels of messenger  receptors
Up-regulation:  levels of messenger  receptors
Supersensitivity: 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 γ-GDP
G proteins transmit signals from >1000 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
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