Classification of Membrane Receptors
A signaling molecule, or primary messenger (e.g., a peptide hormone), typically does not enter the cell. Instead, it binds to a specific membrane receptor. Based on their mechanism of action, receptors are divided into three main groups:
- Ionotropic (ligand-gated ion channels): contain a subunit that binds the signaling molecule and forms an ion channel. A classic example is the nicotinic acetylcholine receptor at the postsynaptic membrane.
- Catalytic (enzyme-linked): possess intrinsic enzymatic activity that is activated upon ligand binding. For example, the insulin receptor has intrinsic tyrosine kinase activity.
- Metabotropic (GPCRs — G protein-coupled receptors): transmit signals to intracellular target enzymes (such as adenlyl cyclase or phospholipase C) via membrane-bound G proteins. This group includes adrenergic and glucagon receptors.
Secondary Messengers
Secondary (intracellular) messengers are low-molecular-weight molecules characterized by high diffusion rates in the cytosol. Their concentration changes in response to primary hormone binding to its receptor. Their primary role is to alter the activity of cytosolic proteins.
Key secondary messengers:
- cAMP (cyclic adenosine-3',5'-monophosphate) — synthesized from ATP by adenylate cyclase.
- IP₃ (inositol-1,4,5-trisphosphate) — derived from the membrane phospholipid PIP₂ via phospholipase C action. Opens calcium channels on the endoplasmic reticulum.
- Ca²⁺ (calcium ions) — released into the cytosol under the influence of IP₃.
- DAG (diacylglycerol) — functions synergistically with calcium.
- cGMP (cyclic guanosine-3',5'-monophosphate).
G Protein-Coupled Signal Transduction Systems
The interaction of a hormone with serpentine (7-transmembrane domain) receptors triggers one of two major signal transduction pathways. In both systems, the activity of the membrane enzyme is terminated due to the intrinsic GTPase activity of the G protein $\alpha$-subunit (hydrolysis of GTP to GDP).
| Feature | Adenylate Cyclase System | Inositol Phosphate System |
|---|---|---|
| Messenger Examples | Glucagon, epinephrine (via $\beta$-receptors) | Vasopressin, angiotensin II, epinephrine ($\alpha_1$) |
| G Protein Type | $G_s$ protein ($\alpha$-subunit) | $G_q$ protein ($\alpha$-subunit) |
| Effector Enzyme | Adenylate cyclase | Phospholipase C |
| Secondary Messengers | cAMP | IP₃, DAG, $Ca^{2+}$ |
| Target Enzyme | Protein kinase A (PKA) | Protein kinase C (PKC), calmodulin |
| Messenger Clearance | Hydrolysis of cAMP by phosphodiesterase | Dephosphorylation of IP₃, reuptake of $Ca^{2+}$ into ER |
Types of Hormone-Cell Interactions
A physiologically significant difference in hormone action lies in the speed and duration of the resulting response, which directly depends on receptor localization:
- Membrane Receptors: characteristic of peptide hormones that cannot cross the cell membrane. The response develops rapidly, but the effect is short-lived.
- Intracellular Receptors: characteristic of steroid and thyroid hormones. These molecules easily cross the lipid bilayer. The response develops slowly, but persists for a long time.