Cylic GMP, NO, and Sensory Reception

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Cylic GMP, NO, andSensory Reception
Lecture 28 BSCI 420/421 Nov 2002 1.
cGMP Vision 2. NO cGMP 3. Olfaction
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1. cGMP Vision Vertebrate visual receptors are
specialized cells called rods (dim light B W
vision) and cones (color vision). The discs
(1000) in the outer segment contain the
photosensitive protein rhodopsin. Rhodopsin is a
7-pass, G-protein -linked receptor for light
instead of a soluble signal molecule.
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1. When light hits the rhodopsin, the
chromophore, a Vit A derivative called 11-cis
retinal, is converted to all-trans retinal, and
changes the shape of the opsin (protein) part of
rhodopsin. 2. This causes the G-protein (called
transducin) to bind GTP, and alpha to separate
from beta/gamma. 3. Ga activates the enzyme cGMP
phosphodiesterase. cGMP GMP
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4. This decrease in cGMP decreases the amount of
cGMP bound to membrane Na channels, and the
cGMP-gated Na channels close. 5. This
hyperpolarizes the PM, reducing the amount of
inhibitory transmitter released and the effect is
to allow the optic nerves to fire.
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Signal amplification in G-protein linked signal
system. G -gt Enzyme -gt 2nd
mess.-gt Regulated protein-gt Macro level
response
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2. NO cGMP Guanylyl cyclase can be regulated by
the gas nitric oxide (NO). Because a gas, it can
pass right thru the PM and bind dir. to GC
without a surface receptor. An important fx is to
cause smooth muscle relaxation
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This causes blood vessels to relax. In angina,
Nitroglycerine -gt NO, which causes heart blood
vessels to relax and increases blood flow thru
them. NO released by nerves in the penis cause
blood vessel dilation and erection. (Viagra
inhibits cGMP phosphodiesterase, which converts
cGMP to GMP) And activated macrophages and
neutrophils release NO to cause local swelling in
presence of pathogens. CO can also bind to GC
and increase cGMP.
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3. Olfaction - also depends on G-protein-linked
receptors. Olfactory receptors are on modified
cilia of olfactory neurons. Olfactory epithelium
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Receptors bind odorant molecules and release
specific Golf alpha subunits that activate
adenylyl cyclase. The increase in cAMP opens
cAMP-gated Na channels . This depolarizes the
cell and initiates an action potential that
travels down the axon to the brain and excites a
cell that interprets this as a particular
molecule or type of odorant. The basis for
discrimination? Each olfactory receptor cell
contains only one receptor type, but there are
about 1000 different receptor types cells. The
brain interprets each cell as having detected a
diff odorant molecule. The frequency of spikes
signals the concentration or intensity of the
odorant molecules.