Substance P – it’s a neurotransmitter, but what does it do?
New discoveries, be they hitherto undescribed plants or animal species, new subatomic particles, new chemical compounds…., whatever: it’s got to have a name. C.W. Roentgen called “his” rays X-rays; bosons and fermions (they are subatomic particles) are named after the Indian Satyendra N. Bose and Italian-born Enrico Fermi. Einsteinium is named after German-born Albert Einstein and the names of other chemical elements are often of Greek origin. Brain waves are simply called alpha, beta, gamma or delta waves. Not very inventive I’d say, just like the vitamins’ names A, B, C, D are. And this brings me to Substance “P”.’
Why is it called that? I don’t know, but it’s a peptide neurotransmitter and I heard a lot about it (and another peptide neurotransmitter known as “somatostatin”) from my former colleague in New Zealand Lance McLeay. Lance occupied himself with gastrointestinal motility, basically how the intestine behaves when it has to digest something. Who or what exerts control over the gut’s movement was his main research interest and that’s where neurotransmitters come in. When I was a physiology student years ago, everybody talked about acetylcholine, GABA and glutamate neurotransmitters, but nowadays at least 200 of them are known. And Substance P, discovered by Ulf von Euler in 1931, was shown to be one of them.
Neurotransmitters are small molecules that act as ‘messengers’, but unlike hormones, which are also chemical messengers, but released into the blood and acting on target organs often far away, neurotransmitters are not released into the blood and do not travel long distances. They are stored in tiny vesicles and released from the terminal “buttons” of a nerve cell into an approximately 20 nm wide extracellular gap that separates the nerve cell from another neuron, a gland or a muscle cell on what is called “the postsynaptic side” of the gap. (The gap itself is known as a chemical synapse and consists of a pre- and postsynaptic side). We owe the discovery of the synapses to the Spanish Nobel laureate Ramon y Cajal, who showed at the beginning of the 20th century, using Golgi’s famous silver stain method, that nerve cells had long fibrous extensions known as axons, which formed connections with each other as well as muscle and glandular cells.
Once a neurotransmitter is released it crosses the narrow extracellular gap by diffusion and acts upon (but not enter) the postsynaptic cell, which will or won’t act upon it (depending on the nature and/or amount of neurotransmitter released). Now in case of our Substance P and somatostatin, the two neurotransmitters act antagonistically: they hinder each other. This can be seen very well in preparations with diabetic animals, in which an increase in gastric somatostatin suppresses gut motility (and thus the liberation of gastrointestinal hormones) but parallel to that a decrease in gastric Substance P concentration is observed. Obviously, somatostatin influences Substance P and Substance P influences somatostatin, which is why elevated levels of SP can lead to heightened gut motility and diarrhoea, especially in cases of gut inflammations. In inflammations somatostatin is a selective antagonist of substance P, the latter being considered pro-inflammatory and also critically involved in other situations of stress and even mood disorders, mediating pain and vomiting and possibly acting as a vasodilator.
I met Professor von Euler, who received the Nobel prize in Physiology in 1970, once at a conference and should have asked him whether he called his substance “P” because it was a peptide, or because he discovered it in a powderous preparation. But I didn’t dare. I was a young and shy scientist at that time and even missed the chance to get an autograph from the famous man. That’s something I do now regret.
© Dr V.B. Meyer-Rochow and http://www.bioforthebiobuff.wordpress.com, 2019.
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