Classification of membrane receptors
A signaling molecule, or primary messenger (e.g., a peptide hormone), typically does not penetrate inside the cell. It binds to a specific receptor on the membrane. Depending on the mechanism of action, there are three main groups of receptors:
- Ionotropic (channel-forming): contain a subunit that binds the signaling molecule and forms an ion channel. A typical example is the acetylcholine receptor on the postsynaptic membrane.
- Catalytic: possess intrinsic enzymatic activity that manifests after ligand binding. For example, the insulin receptor has tyrosine kinase activity.
- Metabotropic (GPCR — G-protein-coupled receptors): transmit the signal to intracellular target enzymes (adenylyl cyclase or phospholipase C) with the participation of membrane G-proteins. This group includes adrenaline and glucagon receptors.
Secondary messengers
Secondary (intracellular) messengers are low-molecular-weight molecules with a high diffusion rate in the cytosol. The concentration of these substances changes in response to the binding of the primary hormone to the receptor. Their main task is to alter the activity of cytosolic proteins.
Key secondary messengers:
- cAMP (cyclic adenosine 3',5'-monophosphate) — formed from ATP by the action of adenylyl cyclase.
- IP₃ (inositol 1,4,5-trisphosphate) — formed from the membrane phospholipid PIP₂ by the action of phospholipase C. It opens endoplasmic reticulum (ER) calcium channels.
- Ca²⁺ (calcium ions) — released by the action of IP₃.
- DAG (diacylglycerol) — works in tandem with calcium.
- cGMP (cyclic guanosine 3',5'-monophosphate).
G-protein coupled signaling systems
The interaction of a hormone with serpentine receptors (7-TMS) triggers one of two main signal transduction systems. In both systems, the activity of the membrane enzyme is decreased due to the GTPase activity of the $\alpha$-subunit of the G-protein (GTP is hydrolyzed to GDP).
| Characteristic | Adenylate cyclase system | Inositol phosphate system |
|---|---|---|
| Examples of messengers | Glucagon, adrenaline (via $\beta$-receptors) | Vasopressin, angiotensin II, adrenaline ($\alpha_1$) |
| Type of G-protein | $G_s$-protein ($\alpha$-subunit) | $G_q$-protein ($\alpha$-subunit) |
| System enzyme | Adenylyl cyclase | Phospholipase C |
| Secondary messengers | cAMP | IP₃, DAG, $Ca^{2+}$ |
| Target enzyme | Protein kinase A (PKA) | Protein kinase C (PKC), calmodulin |
| Decrease in messenger concentration | Hydrolysis of cAMP by the enzyme phosphodiesterase | Dephosphorylation of IP₃, pumping of $Ca^{2+}$ into the ER |
Types of hormone-cell interactions
A physiologically important difference in hormone action lies in the speed and duration of the generated response. This directly depends on the receptor localization:
- Membrane receptors: characteristic of peptide hormones that do not penetrate into the cell. The response to their action develops rapidly, but the effect is short-lived.
- Intracellular receptors: characteristic of steroid and thyroid hormones. These molecules freely pass through the lipid bilayer. The response to their binding develops slowly, but persists for a long time.
Briefly: answers to topical questions
Which neurotransmitters and hormones act via ionotropic receptors?
The following neurotransmitters act via ionotropic receptors (hormones are not mentioned in this context):
- Acetylcholine — acts via nicotinic acetylcholine receptors (in cholinergic and neuromuscular synapses).
- GABA — interacts with GABA_A receptors, opening chloride channels and causing membrane hyperpolarization.
- Glycine — acts via glycine receptors by a mechanism similar to GABA.
What is the structure of the membrane G-protein?
The provided materials describe only the presence of the alpha subunit in the G-protein structure.
- $\alpha$-subunit — possesses GTPase activity (performs GTP hydrolysis to GDP), which causes a decrease in the activity of the signaling system enzyme.
Depending on the type ($G_s$ or $G_q$), the $\alpha$-subunit acts as a protein that activates an enzyme (adenylyl cyclase or phospholipase C).
What specific function does diacylglycerol (DAG) perform in signal transduction?
The main function of diacylglycerol (DAG) is to activate the enzyme protein kinase C (PKC).
- Enzyme binding — DAG occupies specific sites in protein kinase C.
- Affinity change — DAG binding further increases the affinity of protein kinase C for calcium ions.
As a result, an active quaternary complex (PKC · $Ca^{2+}$ · PS · DAG) is formed on the inner side of the membrane, which phosphorylates specific intracellular enzymes.
The connection between enzymes and kinases can be remembered by their initial letters: the enzyme Adenylyl cyclase activates protein kinase A, and Phospholipase C (via secondary messengers) activates protein kinase C.
Class and exam questions
What is the difference between the effects of intracellular and membrane receptors?
Intracellular receptors (for steroid and thyroid hormones) produce a slow but prolonged effect. Membrane receptors (for peptide hormones) provide a rapid but short-lived response.
How is the adenylyl cyclase system inactivated?
The membrane enzyme is turned off due to the GTPase activity of the G-protein alpha subunit. The secondary messenger itself (cAMP) is degraded to AMP by the enzyme phosphodiesterase.
What is the function of the second messenger $IP_3$?
Inositol 1,4,5-trisphosphate (IP3) opens calcium channels of the endoplasmic reticulum (ER), leading to a sharp increase in the concentration of calcium ions in the cell cytosol.
What else to study on this topic
- Structure and functioning of 7-TMS (serpentine) receptors
- Activation and inactivation cycle of the G-protein alpha subunit
- Mechanism of protein kinase A activation and phosphorylation of target proteins
- Role of phosphodiesterase in the regulation of cyclic nucleotide levels
- Calmodulin and calcium-dependent enzyme cascades
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