Control of Cells by Chemical Messengers
135
III. Water-soluble messengers bind to receptors on the plasma
membrane. The pathways induced by activation of the
receptor often involve second messengers and protein
kinases.
a. The receptor may be a ligand-gated ion channel. The
channel opens, resulting in an electrical signal in the
membrane and, when calcium channels are involved, an
increase in the cytosolic calcium concentration.
b. The receptor may itself be an enzyme. With one
exception, the enzyme activity is that of a protein kinase,
usually a tyrosine kinase. The exception is the receptor
that functions as a guanylyl cyclase to generate cyclic
GMP.
c. The receptor may activate a cytosolic JAK kinase
associated with it.
d. The receptor may interact with an associated plasma
membrane G protein, which in turn interacts with plasma
membrane effector proteins—ion channels or enzymes.
e. Very commonly, the receptor may stimulate, via a Gs
protein, or inhibit, via a Gi protein, the membrane
effector enzyme adenylyl cyclase, which catalyzes the
conversion of cytosolic ATP to cyclic AMP. Cyclic AMP
acts as a second messenger to activate intracellular cAMP-
dependent protein kinase, which phosphorylates proteins
that mediate the cell’s ultimate responses to the fi rst
messenger.
f. The receptor may activate, via a G protein, the plasma
membrane enzyme phospholipase C, which catalyzes
the formation of diacylglycerol (DAG) and inositol
trisphosphate (IP
3
). DAG activates protein kinase C, and
IP
3
acts as a second messenger to release calcium from the
endoplasmic reticulum.
IV. The receptor, via a G protein, may directly open or close
(gate) an adjacent ion channel. This differs from indirect G-
protein gating of channels, in which a second messenger acts
upon the channel.
V. The calcium ion is one of the most widespread second
messengers.
a. An activated receptor can increase cytosolic calcium
concentration by causing certain calcium channels in the
plasma membrane and/or endoplasmic reticulum to open.
Voltage-gated calcium channels can also infl uence
cytosolic calcium concentration.
b. Calcium binds to one of several intracellular proteins,
most often calmodulin. Calcium-activated calmodulin
activates or inhibits many proteins, including calmodulin-
dependent protein kinases.
VI. Arachidonic acid is released from phospholipids in the
plasma membrane to act as a unique type of second
messenger. Eicosanoids are derived from the fatty acid
arachidonic acid. They exert widespread intra- and
extracellular effects on cell activity.
VII. The signal transduction pathways triggered by activated
plasma membrane receptors may infl uence genetic expression
by activating transcription factors. In some cases, the primary
response genes (PRGs) infl
uenced by these transcription
factors code for still other transcription factors. This is
particularly true in pathways initiated by fi rst messengers that
stimulate their target cell’s proliferation or differentiation.
VIII. Cessation of receptor activity occurs when the fi rst
messenger molecule concentration decreases or when the
receptor is chemically altered or internalized, in the case of
plasma membrane receptors.
KEY TERMS
adenylyl cyclase
128
affi nity
122
agonist
123
antagonist
123
arachidonic acid
131
calmodulin
131
calmodulin-dependent protein
kinase
131
cAMP-dependent protein
kinase
128
cGMP-dependent protein
kinase
126
competition
122
cyclic AMP (cAMP)
128
cyclic endoperoxide
131
cyclic GMP (cGMP)
126
cyclooxygenase (COX)
132
diacylglycerol (DAG)
130
down-regulation
123
eicosanoid
131
fi rst messenger
126
G protein
127
G-protein-coupled receptor
127
guanylyl cyclase
126
inositol trisphosphate (IP
3
)
130
internalization
123
JAK kinase
126
leukotriene
131
ligand-gated ion channel
126
lipoxygenase
132
phosphodiesterase
128
phospholipase A
2
132
phospholipase C
130
primary response gene
(PRG)
133
prostaglandin
131
protein kinase
126
protein kinase C
130
receptor (for messengers)
121
receptor activation
123
receptor protein
121
receptor tyrosine kinase
126
saturation
122
second messenger
126
signal transduction
pathway
124
specifi city
121
steroid-hormone receptor
superfamily
124
supersensitivity
123
thromboxane
131
transcription factor
124
up-regulation
123
CLINICAL TERMS
aspirin
133
nonsteroidal anti-infl ammatory drug (NSAID)
133
REVIEW QUESTIONS
1. What is the chemical nature of receptors? Where are they
located?
2. Explain why different types of cells may respond differently to
the same chemical messenger.
3. Describe how the metabolism of receptors can lead to down-
regulation or up-regulation.
4. What is the fi rst step in the action of a messenger on a cell?
5. Describe the signal transduction pathway that lipid-soluble
messengers use.
6. Classify plasma membrane receptors according to the signal
transduction pathways they initiate.
7. What is the result of opening a membrane ion channel?
8. Contrast receptors that have intrinsic enzyme activity with
those associated with cytoplasmic JAK kinases.
9. Describe the role of plasma membrane G proteins.
10. Draw a diagram describing the adenylyl cyclase-cAMP system.
11. Draw a diagram illustrating the phospholipase C/DAG/IP
3
system.
12. What are the two general mechanisms by which fi rst messengers
elicit an increase in cytosolic calcium concentration? What are
the sources of the calcium in each mechanism?
13. How does the calcium-calmodulin system function?
14. Describe the manner in which activated plasma membrane
receptors infl uence gene expression.
previous page 163 Vander's Human Physiology The Mechanisms of Body Function read online next page 165 Vander's Human Physiology The Mechanisms of Body Function read online Home Toggle text on/off