Which ligands bind to cell surface receptors, such as adrenaline (epinephrine) and noradrenaline (norepinephrine)?

Catecholamines Bind to Cell Surface Receptors

Among the listed ligands, only catecholamines (option b) bind to cell surface receptors.

Mechanism of Ligand-Receptor Binding

Catecholamines like epinephrine (adrenaline) and norepinephrine (noradrenaline) interact with cell surface receptors through a specific binding mechanism:

• Catecholamines bind to adrenergic receptors, which are cell surface glycoproteins that belong to the G protein-coupled receptor (GPCR) superfamily 1
• These receptors are embedded in the plasma membrane and recognize the catecholamines released from sympathetic nerve endings and the adrenal medulla 1
• The FDA drug labels for epinephrine and norepinephrine confirm that these catecholamines act on alpha (α) and beta (β) adrenergic receptors located on the cell surface 2, 3

Types of Adrenergic Receptors

Catecholamines bind to several subtypes of adrenergic receptors on the cell surface:

• α1 receptors: Coupled to stimulatory Gq proteins, activate phospholipase C, primarily found in vascular smooth muscle 4
• α2 receptors: Coupled to inhibitory Gi proteins, inactivate adenylyl cyclase 4
• β1 receptors: Predominate in the heart, activate the Gs-adenylyl cyclase-cAMP-protein kinase A signaling cascade 4
• β2 receptors: Widely distributed but predominantly in bronchial smooth muscle, activate adenylyl cyclase 4
• β3 receptors: Found in adipose tissue, can couple to both stimulating and inhibiting G proteins 4

Why Other Options Are Incorrect

1. Steroids (option a): Steroids do not bind to cell surface receptors. As lipid-soluble molecules, they diffuse across the cell membrane and bind to intracellular receptors 5.

2. Retinoids (option c): Similar to steroids, retinoids are lipid-soluble and bind to intracellular receptors, not cell surface receptors.

3. Thyroid hormones (option d): Thyroid hormones are also lipid-soluble and primarily act by binding to nuclear receptors inside the cell. According to the Praxis Medical Insights, only about 0.03% of thyroid hormone (T4) remains free 5.

4. Vitamin D (option e): Vitamin D metabolites, like 25OHD, are lipid-soluble and bind to intracellular receptors, not cell surface receptors. Only about 0.03% of vitamin D metabolites remain free 5.

Importance of Cell Surface Receptor Binding

The binding of catecholamines to cell surface receptors is crucial for:

• Transducing external catecholamine stimulus into intracellular signals 1
• Mediating sympathetic nervous system actions, including cardiovascular responses 1
• Regulating various physiological processes such as blood pressure, heart rate, and smooth muscle contraction 4

Cell surface receptor binding allows for rapid signal transduction and response to changing physiological conditions, which is essential for the "fight or flight" response mediated by catecholamines 4.