In this video Dr. Goldstein explains how chemical messengers are synthesized and function throughout the autonomic nervous system.
The autonomic nervous system works by way of chemical messengers. There’re different chemical messengers and one of the more important families of chemical messengers is catecholamines. This is an area that has been of interest to me for many years. The catecholamines are key chemical messengers both in the brain and in all the organs of the body.
It’s important to realize that a key aspect of autonomic function is neurotransmission. Chemical messengers are released from nerves and have key effects. The general arrangement is shown here. In response to nerve traffic there’s release of a transmitter that’s being stored in bubble-like spheres called vesicles, and the chemical messenger reaches the target organ and causes cellular activity. Because of the changes, like just say in blood pressure and so forth, there’s afferent traffic to the brain which affects the efferent traffic and so you have this cycle and it’s a negative feedback loop. Negative feedback just means here is a positive effect, here is a negative effect and any time you’ve got a cycle like this where there’s an odd number of negative signs, that’s a negative feedback loop, the level of the monitored variable, let us just say blood pressure, is going to be held stable. Negative feedback loop.
Norepinephrine, which is the key chemical messenger neurotransmitter of the sympathetic noradrenergic system, is made in vesicles. It’s made inside the vesicles in the sympathetic nerve terminals. I guess she already knows everything And a key enzyme is dopamine beta hydroxylase or DBH. There are rare patients who have a lack of dopamine beta hydroxylase. Because of that, the person can’t make norepinephrine. Because of that there are all sorts of effects on that part of the autonomic nervous system but here is a quiz question for you. If you had a patient with DBH deficiency, would that patient be able to sweat? Yes, because you don’t need norepinephrine to sweat. That was the sympathetic cholinergic system to a large extent. So, acetylcholine is a chemical messenger there. It’s not quite that simple but the fact of the matter is that people with DBH deficiency do sweat. Here is a beautiful image provided by Risa Isonaka showing either vesicles or clusters of vesicles (we haven’t figured that out) in human sympathetic neuron. This is inside the ganglion.
Exocytosis is important, so I just want to go over how the chemical messenger gets out. The chemical messenger gets out because the vesicle physically, physically goes to the membrane surface and then pourates, right here, and then the soluble contents come out. That’s how chemical neurotransmission happens. So, if you look under an electron microscope, you can actually see these little omega signs, it means the pourated vesicles that are fused with the membrane surface, but the vast majority of vesicles are not pourated, only a teeny amount of the storage transmitter is released under normal circumstances.
David S. Goldstein, M.D., Ph.D
Chief, Autonomic Medicine Section
NINDS, National Institutes of Health