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Paracrine Signaling

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Paracrine Signaling

Cells can communicate, one to another, in several distinct ways. One of the most important ways is paracrine signaling, the topic of this lesson. There are examples of paracrine signaling all over the human body, and indeed, examining certain molecular pathways in our bodies is one of the best ways of understanding the mechanism of this form of cell signaling. Paracrine signaling helps to alter features of our blood vessels, as well as other organs. Let's look at some of these examples.

Definition of paracrine signaling/secretion

Paracrine signaling, also known as paracrine secretion, is a form of cellular signaling in which cells communicate over relatively short distances by the release (secretion) of small signaling molecules onto nearby cells. The nearby target cells then react to this signal in some way, producing an effect.

We can use this definition to come up with the key features of paracrine signaling:

Key Features of Paracrine Signaling

  • It is a form of cell signaling

  • It happens via the release of small molecules

    • An example of one is nitric oxide; we'll talk about it more below.

  • It occurs between cells (individual or groups) that are close in proximity to one another

    • There is a short distance between the cells that secrete or release the signals and the target cells that are altered by these signals.

Definition of paracrine factors

These small signaling molecules we will discuss throughout this lesson also have another name. They are called paracrine factors, and they are distinguished by their ability to travel short distances and then enter target cells. Often times paracrine factors enter target cells by diffusion, but there are other methods of entry as well, some of which include receptor-binding.

Example of paracrine signaling

As promised, here is an in-depth example of paracrine signaling, using the signaling molecule nitric oxide (chemical formula = NO). While you may be more familiar with it from general chemistry, nitric oxide is also a really important molecule in our bodies (in biology and physiology). Our blood vessels are hollow tubes, and the walls of these tubes are actually comprised of several layers. The outermost layer is known as the adventitia, which is often fibrous and made of different kinds of collagen. The middle layer is muscular, known as the media, and is comprised of smooth muscle. Finally, the innermost layer, which is the last layer before the hollow center, is called the intima, and the thin film of cells that lies atop is called the endothelium (Fig. 1).

Paracrine signaling layers of blood vessels ohio state universityFigure 1: Layers of blood vessels. Ohio State University.

How does all this relate to paracrine signaling? Well, one of the functions of the endothelium is to produce none other than Nitric Oxide! And nitric oxide produced by the cells of the endothelium then acts as a small signaling molecule diffusing into nearby smooth muscle cells. Nitric oxide causes smooth muscle relaxation in these cells, which leads to blood vessel dilation. Typically this lowers blood pressure, although it can also lead to red cheeks when you blush, penile erection and clitoral tumescence, and even dilation of your bronchi, depending on when and where the nitric oxide release occurs.

Perhaps you've heard of Viagra? It is one of the most recognizable, popular, and highly prescribed drugs the world over. Viagra is given to treat erectile dysfunction, and this medication's method of action is related to our example of paracrine signaling.

How, you ask? Well, Viagra works by increasing nitric oxide production in endothelial cells! All this increased nitric oxide can then act as a paracrine signal, diffusing to nearby smooth muscle cells in the genitals. Nitric oxide causes the smooth muscle cells to relax, leading to increased blood flow within the genitals, which leads to engorgement and corrects the erectile dysfunction.

Nitric oxide has only a very short half-life (lasting about 5 seconds), so only a finite amount of gas can act on a finite number of nearby cells before it all dissipates. This is part of the reason that nitric oxide can act as a paracrine signaling molecule, because it can produce its effects only on nearby target cells, and not on cells that are quite far away. Also, because the mechanism of dispersal of the signaling molecule is simple diffusion, the closer a target cell is, the more likely it is to receive the signal.

Now, we've learned some biological principles and also the physiology behind nitric oxide as a mediator for vasodilation (blood vessel dilation). With all this in mind, let's remind ourselves of how nitric oxide fulfills the criteria for being an agent of paracrine signaling.

  1. Nitric oxide is the signal, it is a small molecule that leads to effects and/or alterations in target cells.

  2. Nitric oxide only travels short distances, to nearby cells.

  3. Nitric oxide is taken up in these cells by diffusion, not through the blood.

Seems like nitric oxide checks out! To hammer these principles home, let's look at another example.

Effect of paracrine signaling

To look at the process of paracrine signaling, we'll use another example. This time, it occurs in our limbs, and it also occurs during our fetal development. I'm talking about the Hedgehog transcription factors. What are transcription factors?

Transcription factors - these are proteins that influence, or even control, the rate and timing of the transcription of a certain gene.

What is a hedgehog besides a cute, prickly animal? In developmental cellular biology, the Hedgehog family (including, sometimes, the sonic hedgehog protein) is a family of proteins that help to order body parts in their right place. It gives organs and organisms their orientations and orderly patterns, and this largely happens in developing fetuses. Hedgehog proteins were best studied in Drosophila fruit flies, and errors in them lead to misshapen fruit flies with eyes where their legs should be, and legs where their eyes should be, and so on.

In you and me, hedgehog proteins are involved in planning everything from our brain positions and patterns, to our guts, to our limbs, to our lungs. This family of proteins helps our organs to be in the right place. In fact, some mutations in sonic hedgehog protein, in particular, can cause holoprosencephaly (when the brain doesn't divide into two hemispheres) which can even lead to cyclopia - having just one eye in the middle of the forehead!

Hedgehog proteins can be secreted by certain cells and bind to cell receptors on nearby cells. This binding causes signal transduction, where certain changes in the target cell occur in response to signal binding. These changes ultimately lead to the proper limbs and organs developing in the right way, in response to their hedgehog signals. For example, the cells that will form the base of the finger might form in response to signal transduction via hedgehog proteins released from cells that will form the palm. And what form of signal transduction is this specifically? Paracrine signaling. These hedgehog proteins must only act over short distances of course, so that they only instruct the cells nearest to them. If they could travel far away from their site of origin, you might have fingers developing on the wrist and elbow, not just the hand.

The difference between autocrines and paracrines

Hopefully by now, we have a great, in-depth understanding of paracrine signaling. So, let's compare it directly to another form of cell communication - autocrine signaling.

First, we must briefly note what autocrine signaling is. This is when a cell releases a signal for itself and then undergoes some changes or alterations due to this signal. The auto- in autocrine means "for self", so this is cell signaling for and by "self", where self is a particular cell.

Autocrine signalingParacrine signaling
Acts onThe same cell it is released byNearby cells via diffusion or transduction
Typical signaling moleculesGrowth factors and cytokinesTranscription factors and neurotransmitters
Typical cell releasing signalWBCsNeurons
When can it go wrongCancer inducing cytokines, causing growth of tumorsCancer inducing sonic-hedgehog proteins

Features of paracrine signaling

Now that we know so much about paracrine signaling, let us recap the factors that give paracrine signaling its distinguishing features as a form of cell signaling.

  1. Paracrine signals only travel short distances

  2. Paracrine signals only affect (relatively) nearby cells.

  3. Paracrine signals are not transmitted through the blood

    • Instead, they diffuse directly or get taken up by receptors to cause signal transduction.

  4. Paracrine signals are very important in localized adjustments in blood vessel dilation: things like blood pressure, genital engorgement, and face flushing.

  5. Paracrine signals are used to help pattern the order and orientation of many species' bodies via transcription factors.

Paracrine Signaling - Key takeaways

  • Paracrine signaling is one of the four forms of cell signaling, including autocrine, endocrine, and direct-contact signaling.
  • Paracrine signaling occurs when small signaling molecules are transmitted to target cells only short distances away, which then undergo some alteration or effect.
  • Nitric oxide mediation of blood vessel dilation utilizes paracrine signaling to control nearby smooth muscle cells' relaxation.
  • Hedgehog proteins utilize paracrine signaling to help determine the orientation and patterns of body organs in animals from fruit flies to human beings.
  • Paracrine signaling occurs on nearby target cells, while autocrine signaling occurs on the same cell that released the signal.

Frequently Asked Questions about Paracrine Signaling

Paracrine signaling is a form of cell communication in which small molecules (signals) are released onto very nearby target cells, without going through the bloodstream.

Small molecules diffuse or get transduced onto/in to target cells, and cause an effect. This process occurs only over short distances.

Paracrine describes a form of cell signaling that occurs only between cells near to each other, and does not occur through the blood.

Autocrine signaling is when a cell releases a signal for ITSELF, while paracrine signaling is when a cell releases a signal for other nearby cells.

Paracrine factors are the small molecules (such as NO) that can diffuse or be transduced to nearby cells to cause an effect.

Final Paracrine Signaling Quiz

Question

What kind of signaling is seen when nitric oxide dilates local blood vessels

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Answer

Paracrine signaling

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Question

While endocrine signaling occurs through the blood, paracrine ____

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Answer

Does not

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Target cells in paracrine signaling are at what distance?

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Nearby

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Question

Hedgehog proteins are _____

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Answer

Transcription factors

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Hedgehog proteins function?

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Answer

Orientation and patterning of body organs (especially limbs)

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Can paracrine signaling molecules directly diffuse, or only be transduced

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Answer

Both

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Question

Paracrine signals act on nearby cells, autocrine signals act on......

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Answer

Self

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Question

Which small molecule, that is a paracrine signaling molecule, is used in the mechanism of action of the drug Sildenafil (Viagra)?

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Answer

Nitric oxide

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Question

Nitric oxide is used for vaso____

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Answer

constriction

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Question

Paracrine signals are secreted into which environment

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Answer

Intracellular

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Question

In which organisms have hedgehog proteins been studied extensively

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Answer

Drosophila, fruit flies

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At one time in an organism's life are sonic hedgehog proteins utilized most?

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Answer

Fetal development

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Paracrine signaling is 

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Extremely common

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Transcription factors often transmit their effects via which type of signaling

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Answer

Paracrine signaling

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How long is the half life of Nitric Oxide?

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Answer

Seconds

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Question

Synaptic signaling is a subtype of

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Answer

Paracrine signaling

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What is the definition of synaptic signaling?

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Answer

 Cell communication where neurons release electrical or chemical signals onto post-synaptic cells, causing effects

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Electrical synaptic signaling is prominent in which type of organisms

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Invertebrates

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Question

What's the other name for the motor endplate?

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Answer

The neuromuscular junction

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What is the name of the neurotransmitter released at the neuromuscular junction?

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Answer

Acetylcholine

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The part of the neuron that releases neurotransmitters into the synapse is

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axon terminal

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The influx of what ion is required for acetylcholine to be released by the axon at the neuromuscular junction?

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Calcium

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If the originating neuron of a neurotransmitter is called the presynaptic neuron, what is the receiving neuron called

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Postsynaptic neuron

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The _____ acetylcholine receptor is found at the muscle cell of the neuromuscular junction?

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Answer

nicotinic acetylcholine receptor

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Question

Name one of the methods that can lead to neurotransmitters leaving the synaptic cleft

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Diffusing away, 

Broken down by scavenger cells, 

Reuptake by the presynaptic neuron

Broken down by enzymes


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Question

In what type of reflexes are electrical synaptic signaling especially important

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Answer

Defensive reflexes

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Question

The ____ potential is another name for the charge that travels down the axon of a neuron

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Answer

Action potential

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Question

Which of these is NOT one of the three components of the motor endplate

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Answer

Neurotransmitter

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Question

Acetylcholine may be low in Alzheimer's Disease. What is one of the functions of acetylcholine? 

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Answer

Facilitates memory, learning, and voluntary muscle movement

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Question

What is the name of the cell type that acts as a scavenger in the nervous system?

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Answer

Glial cell

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