Receptors and Cell Signaling in Plain Language

How cells listen

Cells constantly receive chemical messages. In multicellular organisms the signals include growth factors, hormones and neurotransmitters. [1] To detect them, cells carry proteins called receptors that bind to signaling molecules and start a physiological response. [1]

Receptors are specific. Different receptors respond to different molecules: insulin receptors bind insulin, dopamine receptors bind dopamine, and so on. [1] A cell's mix of receptors depends on its type, which is why one signal can affect some tissues and not others. [1]

Lock and key, with limits

The usual picture is a lock and key: the signal fits the receptor and triggers a response. It is a helpful image, but cells are more complicated. Many receptors are transmembrane proteins, binding a signal outside the cell and passing it inward through a series of molecular switches. [1] There are three main classes of membrane receptor: G-protein-coupled receptors, ion channel receptors and enzyme-linked receptors. [1]

Why peptides usually work from the outside

Peptides are generally unable to cross the cell membrane to reach targets inside the cell. [2] Instead, therapeutic peptides commonly bind cell-surface receptors and trigger effects inside the cell. [2] A review reports that more than 90% of peptides in active clinical development, as counted in 2018, targeted extracellular targets, including G-protein-coupled receptors such as the GnRH and GLP-1 receptors. [2]

Some signals work differently. Receptors inside the cell typically bind molecules that can pass through the membrane, such as steroid hormones like estrogen. [1] This is one reason peptide hormones and steroid hormones behave differently. See hormones vs peptides.

Activators and blockers

A molecule that binds a receptor can do different things:

• An agonist activates the receptor. Leuprolide has the same biological activity as GnRH by activating GnRH receptors. [2]
• An antagonist blocks it. Degarelix binds the GnRH receptor competitively and acts as an antagonist. [2]

The GLP-1 receptor is another example: liraglutide acts as a GLP-1 receptor agonist. [2] Details are in agonists and antagonists and GLP-1 and GIP biology.

What binding does and does not show

Receptor binding in a laboratory is an early step. It supports a mechanism, which is a proposed explanation of how something works, but it does not show that a product helps people. A compound that binds a receptor in cells can still fail in humans because of poor absorption, rapid breakdown, effects on other receptors or lack of benefit. Rapid breakdown is a known problem for natural peptides. [3]

In this library:

• A receptor finding in cells or animals is preclinical (cells or animals only).


• A proposed mechanism is not evidence of benefit without human studies on a clinical outcome.


• Selective binding in a test tube does not guarantee that a product acts only on that target in the body.

For more, see mechanisms vs clinical outcomes.