Of nicotine, cobras, electric fish, Greek philosophers and physical therapy

I have noticed that some of my latest posts have been rather pessimistic. I have talked about some of the things that are wrong with science or science writing. No more pesimism; I think it is time to explore some of the wonderful things that science can give us.
If you are one of my wonderful, loyal and highly discriminating readers, you know that I love anything science, but “my thing” is mainly the biological sciences.
In my previous post I talked a little bit about connections. Science and especially biology are full of those, really interesting ones too! One of the most fascinating things about these connections is that some of them are really unexpected; just look at the title of this post. The “degrees of separation” between nicotine, cobras, electric fish, Greek philosophers and physical therapy are fewer than you’d think.
Let’s start with nicotine. I would be very surprised if you have never heard of it. Nicotine is one of the most abused (legal) drugs and it is for sure one of the most addictive drugs known. Now, addiction is a rather complicated subject with ramifications that go from the biology of human nervous systems to sociological factors. Here of course we’ll just talk about the biology.
Nicotine is a compound found in several types of plants, especially tobacco plants. In a previous post, I explored the concept of plants as producers of psychopharmacological agents. In terms of nicotine’s usefulness to the tobacco plant, most scientists think that nicotine acts as a natural insecticide that protects the plant against pests. Nicotine essentially kills insects.
However, humans are not insects (ex-boyfriends or ex-husbands do not count); why do many humans like nicotine so much? If we want to understand that, we need to understand a little biochemical pharmacology (don’t be scared by the “chemical” part; trust me, it is very interesting!).
If you want to move, your nervous system must send a highly coordinated message to the appropriate muscle groups to initiate motion. Once the message is received by muscle cells, muscle will contract. There is a specific protein on muscle cells whose main job is to receive this signal from the nervous system and start a series of events that result in muscle contraction. This protein is called the nicotinic acetylcholine receptor (nAChR or nicotinic receptors for short).
The compound that naturally activates this receptor is called acetylcholine and is the first and best-known example of a class of molecules called neurotransmitters. A wide variety of neurotransmitters control many aspects of nerve and muscular physiology, including aspects of brain function. In the same way that acetylcholine is the best-known neurotransmitter, the nicotinic acetylcholine receptor is the best known neurotransmitter receptor.
I am sure that at this point you may have noticed the “nicotinic” as the “first name” of this receptor. This is because nicotine is an activator of this receptor, just as acetylcholine, only more potent. In addition to muscle, there are versions of nicotinic acetylcholine receptors that are found in the human brain, where they seem to be related to learning and memory, as well as diseases such as epilepsy and Alzheimer’s disease among others. Part of the reason why nicotine is so addictive is that it selectively activates nicotinic receptors in the brain, producing pleasurable sensations. This activation of the receptor population oftentimes lead to an increased production of the receptor in the brain, requiring more nicotine to induce the pleasant sensations and it kind of snowballs from there.
How do we know so much about this receptor? I’m glad you asked… (:-)…
We have all heard about cobras. It is possible that the first time you heard about them was by reading Kipling’s Rikki-Tikki-Tavi (1894). This is the story of a brave young mongoose, Rikki-Tikki-Tavi, who defends his adopted human family from two evil cobras, Nag and Nagaina. We all know that cobras have venom; what not everybody knows is that one of the main components of cobra venom targets nicotinic receptors. When a cobra bites a mouse, its venom paralyzes the mouse by blocking the receptor’s activation, preventing the prey’s escape while at the same time killing it by inactivating the muscles required for breathing.
So, we now have the first link that relates nicotine and cobras; they share a common target, our good friends the nicotinic receptors. Incidentally, one of the reasons why mongooses are so adept at killing cobras is because they have a mutation in their nicotinic receptors that makes them more resistant to cobra venom. Interestingly, cobras have nicotinic receptors too as any other vertebrate does. They are also immune to their own venom (this makes sense after all) because their nicotinic receptors also have a mutation that makes them resistant and their mutation is strikingly similar to the one present in mongooses!
I love biology…
Have you ever heard of electric fish? I am sure you have. There are various types of fish that produce electricity for various purposes. The best known ones are electric rays that live in the ocean and the electric eels of the Amazon river. The electric rays and electric eels are able to generate voltages in the range of 200 and about 400 Volts respectively. How do they do that? Well, they have specialized organs called electric organs. These are modified muscles that display cells organized in a battery-like arrangement. In addition to that, they have a really high concentration of nicotinic receptors! These properties have been fully taken advantage of by biochemical pharmacologists. You see, the high amount of the receptor in electric organ allows for the chemical purification of the protein and therefore biochemists can do all kind of tests with them. In fact, the original isolation of the receptor was achieved by biochemically combining a preparation of electric organ with a purified cobra venom component!
All right, so far we have connected nicotine, cobra venom and electric fish.
What about Greek philosophers and physical therapy?
One of the techniques that physical therapists use to treat patients with muscle spasms or pinched nerves is to apply an electrical current to the affected area in a series of treatments. If properly given, these treatments are very effective to alleviate pain.
There are very few topics in the history of science where Greek philosophers are not involved in one way or another. These guys are everywhere! Two of the most famous ones, Plato and Aristotle, talked about the use of bioelectricity to treat pain and other maladies. Of course, they did not explain it in terms of bioelectricity, since the concept of biology as a topic of study did not exist yet. Also, they knew nothing about electricity. However, they wrote on the use of marine rays of the Torpedo genus, which we know today that they are electric fish, to treat headaches and pain caused by arthritis and gout.
How did they do it? Easy, they just stepped on the fish.
And there you have it; we have connected nicotine, cobra venom, electric fish, Greek philosophers and physical therapy, and we did it in less than the proverbial six degrees!
These connections are more than mere curiosities. As fascinating as they are by themselves, they help illustrate why research, any research is important and potentially useful.
Also, you have to admit that it is really, really fun to think about these things.
(:-)
nic
Picture credits:
Dr. O.R. Pagán
http://kidspast.com/world-history/0072B-plato.php
http://eol.org
http://bostonsportsmed.com/electric-stimulation-physical-therapy/

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0 Comments

  1. I did enjoy reading your post–and I am somewhat curious as to why you chose to write about the subjects? Other than the interconnectedness–
    However, I do recall from my days in the herbicide industry that tobacco is (or was) the most researched plant on Earth. And, it is rather enlightening to why nicotine has become so intertwined with our culture.

  2. Thanks! Yes, the topics are kind of all over the place indeed.
    The thing is that I worked on the electric ray nicotinic receptors for about 10 years and in fact, they were the topic of my MS thesis. I used to buy the electric organ from specialized fish suppliers, biochemically isolated the receptor and characterized and quantified them with a radioactively-labeled cobra-like venom component… then I did my experiments.
    As for the philosophers/history/physical therapy thing, for my thesis I read a lot of background material and more recently for a project that I am working on right now, I went back to the literature to become familiar again with the topic, as it’s been some years since I did my MS…
    Tobacco is still quite intensively studied. There are even compounds that are found there that can counteract the effects of nicotine in mammals! I spoke a little bit about them in my post “The mysterious cembranoids”. This is a fascinating area that began to be developed by the people I used to work with and even though is not my main area of research, I am still collaborating with them. (:-)

Thanks for your comment. I will do my best to reply soon; be nice!