Cylic GMP, NO, andSensory Reception

Lecture 28 BSCI 420/421 Nov 2002

1. cGMP & Vision2. NO & cGMP3. Olfaction

1. cGMP & Vision

Vertebrate visual receptors are specialized cells calledrods (dim light B & W vision)and cones (color vision).

The discs (~1000) in the outersegment contain the photosensitive protein rhodopsin.

Rhodopsin is a 7-pass, G-protein-linked receptor for light insteadof a soluble signal molecule.

1. When light hits the rhodopsin, the chromophore, a Vit Aderivative called 11-cis retinal, is converted to all-transretinal, and changes the shape of the opsin (protein) partof rhodopsin.

2. This causes the G-protein (called transducin) to bind GTP,and alpha to separate from beta/gamma.

3. Gactivates the enzyme cGMP phosphodiesterase.

cGMP:

GMP

4. This decrease in cGMP decreases the amount of cGMPbound to membrane Na+ channels, and the cGMP-gatedNa+ 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.

Signal amplification inG-protein linked signal system.

G ->

Enzyme ->

2nd mess.->

Regulated protein->

Macro level response

2. NO & cGMPGuanylyl cyclase can be regulated by the gas nitric oxide (NO).Because a gas, it can pass right thru the PM and bind dir. toGC without a surface receptor.An important fx is to cause smooth muscle relaxation:

This causes blood vessels to relax.

In angina, Nitroglycerine -> NO, which causes heart blood vessels to relax and increases blood flow thru them.

NO released by nerves in the penis cause blood vesseldilation and erection. (Viagra inhibits cGMP phosphodiesterase,which converts cGMP to GMP)

And activated macrophages and neutrophils release NOto cause local swelling in presence of pathogens.

CO can also bind to GC and increase cGMP.

3. Olfaction - also depends on G-protein-linked receptors.

Olfactory receptors are on modified cilia of olfactory neurons.

Olfactory epithelium:

Receptors bind odorant molecules and release specificGolf 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 thatinterprets 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.