biology

Substance P

Substance P is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Substance P rather than just read about it. In short: Substance P (SP) is a neuropeptide, belonging to the tachykinin family of neuropeptides that acts as a neurotransmitter and a neuromodulator. Substance P and the closely related neurokinin A (NKA) are produced from a polyprotein precursor after alternative splicing of the preprotachykinin A gene.

Key takeaways

Substance P belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Substance P to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Substance P from memory before moving on to harder problems.

Reference excerpt

Substance P (SP) is a neuropeptide, belonging to the tachykinin family of neuropeptides that acts as a neurotransmitter and a neuromodulator. Substance P and the closely related neurokinin A (NKA) are produced from a polyprotein precursor after alternative splicing of the preprotachykinin A gene. It is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and has the following sequence:

Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met (RPKPQQFFGLM) with an amide group at the C-terminus. Substance P is released from the terminals of specific sensory nerves. It is found in the brain and spinal cord and is associated with inflammatory processes and pain.

Discovery The original discovery of Substance P (SP) was in 1931 by Ulf von Euler and John H. Gaddum as a tissue extract that caused intestinal contraction in vitro. Its tissue distribution and biologic actions were further investigated over the following decades. The eleven-amino-acid structure of the peptide was determined by Chang, et. al in 1971. In 1983, Neurokinin A (previously known as substance K or neuromedin L) was isolated from porcine spinal cord and was also found to stimulate intestinal contraction.

Receptor The endogenous receptor for Substance P is neurokinin 1 receptor (NK1-receptor, NK1R). It belongs to the tachykinin receptor sub-family of GPCRs. Other neurokinin subtypes and neurokinin receptors that interact with SP have been reported as well. Amino acid residues that are responsible for the binding of SP and its antagonists are present in the extracellular loops and transmembrane regions of NK-1. Binding of SP to NK-1R results in internalization by the clathrin-dependent mechanism to the acidified endosomes where the complex disassociates. Subsequently, SP is degraded and NK-1R is re-expressed on the cell surface. Substance P and the NK1-receptor are widely distributed in the brain and are found in brain regions that are specific to regulating emotion (hypothalamus, amygdala, and the periaqueductal gray). They are found in close association with serotonin (5-HT) and neurons containing norepinephrine that are targeted by the currently used antidepressant drugs. The SP receptor promoter contains regions that are sensitive to cAMP, AP-1, AP-4, CEBPB, and epidermal growth factor. Because these regions are related to complexed signal transduction pathways mediated by cytokines, it has been proposed that cytokines and neurotropic factors can induce NK-1. Also, SP can induce the cytokines that are capable of inducing NK-1 transcription factors.

Function

Overview Substance P ("P" standing for "Preparation" or "Powder") is a neuropeptide – but only nominally so, as it is ubiquitous. Its receptor – the neurokinin type 1 – is distributed over cytoplasmic membranes of many cell types (neurons, glia, endothelia of capillaries and lymphatics, fibroblasts, stem cells, white blood cells) in many tissues and organs. SP amplifies or excites most cellular processes. Substance P is a key first responder to most noxious/extreme stimuli (stressors), i.e., those with a potential to compromise an organism's biological integrity. SP is thus regarded as an immediate defense, stress, repair, survival system. The molecule, which is rapidly inactivated (or at times further activated by peptidases) is rapidly released – repetitively and chronically, as warranted, in the presence of a stressor. Unique among biological processes, SP release (and expression of its NK1 Receptor (through autocrine, paracrine, and endocrine-like processes)) may not naturally subside in diseases marked by chronic inflammation (including cancer).

Vasodilation Substance P is a potent vasodilator. Substance P–induced vasodilation is dependent on nitric oxide release. Substance P is involved in the axon reflex-mediated vasodilation to local heating and wheal and flare reaction. It has been shown that vasodilation to Substance P is dependent on the NK1 receptor located on the endothelium. In contrast to other neuropeptides studied in human skin, Substance P–induced vasodilation has been found to decline during continuous infusion. This possibly suggests an internalization of neurokinin-1 (NK1). As is typical with many vasodilators, it also has bronchoconstrictive properties, administered through the non-adrenergic, non-cholinergic nervous system (branch of the vagal system).

Inflammation SP initiates expression of almost all known immunological chemical messengers (cytokines). Also, most of the cytokines, in turn, induce SP and the NK1 receptor. SP is particularly excitatory to cell growth and multiplication, via usual, as well as oncogenic drivers. SP is a trigger for nausea and emesis. Substance P and other sensory neuropeptides can be released from the peripheral terminals of sensory nerve fibers in the skin, muscle, and joints. It is proposed that this release is involved in neurogenic inflammation, which is a local inflammatory response to certain types of infection or injury.

Pain Preclinical data support the notion that Substance P is an important element in pain perception. The sensory function of Substance P is thought to be related to the transmission of pain information into the central nervous system. Substance P coexists with the excitatory neurotransmitter glutamate in primary afferents that respond to painful stimulation. Substance P and other sensory neuropeptides can be released from the peripheral terminals of sensory nerve fibers in the skin, muscle, and joints. It is proposed that this release is involved in neurogenic inflammation, which is a local inflammatory response to certain types of infection or injury. Unfortunately, the reasons why NK1 receptor antagonists have failed as efficacious analgesics in well-conducted clinical proof of concept studies have not yet been persuasively elucidated.

Mood, anxiety, learning Substance P has been associated with the regulation of mood disorders, anxiety, stress, reinforcement, neurogenesis, synaptic growth and dendritic arborisation, respiratory rhythm, neurotoxicity, pain, and nociception. In 2014, it was found that Substance P played a role in male fruit fly aggression. Recently, it has been shown that Substance P may play a critical role in long-term potentiation of aversive stimuli.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Substance P

Start with the simplest possible case. Write down what Substance P claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Substance P before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Substance P ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Substance P

In research: Substance P appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Substance P in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Substance P is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 7, Hendecapeptides, Neuropeptides, so understanding it makes those chapters shorter.
In everyday life: Look for Substance P outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Substance P in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Substance P means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Substance P out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Substance P in simple terms?

Why does Substance P matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Substance P?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Substance P.