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3
Cell Signaling and
Endocrine Regulation
Figure 3.1
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Types of Cell Signaling
Direct
Signaling cell and target cell connected by gap
junctions
Signal passed directly from one cell to another
Indirect
Signaling cell releases chemical messenger
Chemical messenger carried in extracellular fluid
Some may be secreted into environment
Chemical messenger binds to a receptor on target cell
Activation of signal transduction pathway
Response in target cell
Long distances
Endocrine System
Chemical messenger (hormone) transported by
circulatory system
Nervous System
Electrical signal travels along a neuron and chemical
messenger (neurotransmitter) is released into the
synaptic cleft
Influence postsynaptic cells
Three steps
Release of chemical messenger from signaling cell
(gland)
Transport of messenger through extracellular
environment to target cell
Communication of signal to target cell
Systems for indirect signaling have similarities and
differences
Figure 3.3
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Chemical Messengers
Table 3.2
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Peptide/Protein Hormones
2-200 amino acids long Hydrophilic
Synthesized on the rough Soluble in aqueous
ER solutions
Travel to target cell
Often as larger
dissolved in extracellular
preprohormones fluid
Stored in vesicles Bind to transmembrane
Prohormones receptors
Cut prohormone into Signal transduction
active hormone in Rapid effects on target cell
secretory vesicles Half-life: short half-life
Secreted by exocytosis from few sec. to few hours
Figure 3.4
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Synthesis & Secretion of AVP
Figure 3.5
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Transmembrane Receptor
Figure 3.6
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Steroid Hormones
Figure 3.8
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Amine Hormones
Figure 3.10
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Other Chemical Messengers
Gases
Most act as paracrines
nitric oxide (NO), carbon monoxide , hydrogen sulfide
Nitric oxide: vasodilator: activates intracellular guanylate
cyclase to produce cGMP; PDE terminate NO signal
Hydrogen sulfide: from cysteine; vasodilator to regulate
blood pressure by altering the structure and function of
K+ channels
CO: vasodilator (blood vessels of the heart);
neurotransmitter ( hypothalamo-pituitary axis)
Purines
Function as neuromodulators and paracrines
Bind to purinergic receptors ( transmembrane receptors)
Example: adenosine, AMP, ATP, GTP
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Communication to the Target Cell
Figure 3.13b
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Inactivation of Ligand-Receptor Complex
L-R complex must be inactivated to allow
responses to changing conditions
Figure 3.14
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Signal Transduction Pathways
Convert the change in receptor shape
to an intracellular response
Four components
Receiver
Ligand binding region of
receptor
Transducer
Conformational change of the
receptor
Amplifier
Increase number of molecules
affected by signal
Responder
Molecular functions that
change in response to signal
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Types of Receptors
Intracellular
Bind to hydrophobic
ligands
Ligand-gated ion channels
Lead to changes in
membrane potential
Receptor-enzymes
Lead to changes in
intracellular enzyme
activity
G-protein-coupled
Activation of membrane-
bound G-proteins
Lead to changes in cell
activities
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Intracellular Receptors
Lipid-soluble ligand (
thyroid, steroid) diffuses
across cell membrane
Binds to receptor in
cytoplasm or nucleus
L-R complex binds to
specific DNA sequences (
response elements)
Regulates the
transcription of target
genes
increases or decreases
production of specific
mRNA
Figure 3.18
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Ligand-Gated Ion Channels
Ligand binds to
transmembrane receptor
Receptor changes shape
opening a channel
Ions diffuse across
membrane
Ions move “down” their
electrochemical gradient
Movement of ions
changes membrane
potential
Ligand binds to
transmembrane
receptor
Catalytic domain of
receptor starts a
phosphorylation
cascade
Phosphorylation of
specific intracellular
proteins
Receptor guanylate
cyclase: atrial
natriuretic peptides
(ANPs)
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Receptor Tyrosine Kinases
• Insulin, epidermal
growth factor,
vascular
endothelial growth
factor
• Diabetes mellitus
is due to the defect
in the signal
transduction
pathway
Figure 3.25
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Second Messengers
Table 3.3
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Inositol-Phospholipid Signaling
Figure 3.26
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Cyclic-AMP Signaling
Ex. Glucagon, Adrenocorticotropic Hormone ( ACTH) binds to
receptors in the cell membrane of adrenal cortex for synthesis and
release of glucocorticoid
Figure 3.27
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Interaction Among Transduction Pathways
Set Point
The value of the variable that the body is trying to
maintain
Feedback loops
Positive
Output of effector amplifies variable away from the set
point
Positive feedback loops are not common in physiological
systems
Negative
Output of effector brings variable back to the set point
Pituitary gland
secretes many
hormones
Two distinct
anatomic sections:
Anterior pituitary
(adenohypophysis)
Posterior pituitary
(neurohypophysis)
Figure 3.31
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Regulation of Blood Glucose
Precisely controlled Insulin and glucagon are
Blood glucose too low, secreted by pancreas
brain cannot function
Direct feedback loops
Blood glucose too high,
Pancreas also receives
osmotic balance of blood
neural and hormonal
disturbed
signals
Hormones
Antagonistic pairing
Insulin ( pancreatic beta
cells) lowers blood glucose Hormones that have
levels opposing effects
Glucagon (pancreatic
alpha cells) raises blood
glucose levels
Figure 3.33
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Antagonistic Regulation
Figure 3.34
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Additivity and Synergism
Figure 3.35
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Additivity and Synergism
Additivity
When hormones cause same response in a target cell
Hormones do not use the same signaling pathway
Example: glucagon, epinephrine, and cortisol all raise
blood glucose by different mechanisms
Response of target cell to combinations of these hormones is
additive
Synergism
When hormones enhance effect of other hormones
Response of target cell to combinations of these hormones
more than additive
Permissive Effect
Complete effects of one hormone are dependent on the
presence of another hormone
Figure 3.37
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Control of Glucose and lactate Levels in Arthropods
Crustacean hyperglycemic
hormone (CHH)
Neurohormone from crab
eyestalk
Negative feedback: Secreted
in response to low glucose in
blood/hemolymph
CHH acts via cGMP pathway
Positive feedback: CHH
binds to target cells produce
lactate and release to
circulation which causes the
cells to release more CHH
Figure 3.36
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Adrenal Tissue in Different Vertebrates
Figure 3.38
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Evolution of Cell Signaling