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P, peptide or protein; S steroid; GP, glycoprotein; AA, amino acid derivative.
Polar signaling molecules that are unable to pass the biomembrane through diffusion are recognized by receptors on the cell surface. There are three categories of such receptors (Figure 3.8):
Ion channel‐linked receptors are activated by specific ligands. As a reaction, the conformation of the channel protein is modified, leading to the opening or closure of the channel in question. Ions are let in or out accordingly. The changes in ion concentration produce a change in the membrane potential. In this way, the tension in ion channels can be regulated, or new action potentials released. Ion channel‐linked receptors are mainly found in the neuronal system, such as the nicotinic acetylcholine receptor(nAChR), the GABA receptor, the NMDA receptor, and the glycine receptor.
G‐protein‐coupled receptors (GPCRs) communicate with a G‐protein that is bound either to GTP or GDP. The activation of this type of receptor by a ligand causes a conformation change, which is recognized by the G‐protein. The G‐protein (or, to be more precise, its α‐subunit) is activated and can, in turn, interact with a membrane‐bound effector protein. The effector protein is often an enzyme (adenylyl cyclase or phospholipase), which produces second messengers. This mechanism whereby a single signaling molecule activates a multitude of effector proteins, which, in turn, release a host of second messengers, results in an effective amplification of the signal. Adenylyl cyclase turns ATP into cAMP, which acts as second messenger, regulating protein kinase A allosterically. Once protein kinase A has been activated, it may phosphorylate other enzymes or proteins (e.g. transcription factors), which then spring into action (Figure 3.9). After the dissociation of the α‐subunit, the βγ‐complexes of the activated G‐protein can also be biologically active. In the cardiac muscle, acetylcholine binds to a muscarinic receptor(mAChR), thus activating the βγ‐complex. The βγ‐complex binds to K+ channels and opens them. cAMP is degraded by phosphodiesterase – an enzyme that is considered a target structure for several pharmaceutical products (e.g. caffeine). Table 3.3 gives an overview of some essential hormones that are amplified by adenylyl cyclase and cAMP. A few signal system use cGMP instead of cAMP (e.g. in photoreceptors).
Figure 3.8 Schematic representation of receptor classes on the cell surface. (a) Ion channel‐coupled receptors. (b) G‐protein‐coupled receptors. (c) Enzyme‐coupled receptors (e.g. the tyrosine kinases).
Source: Alberts et al. (2015). Adapted with permission of Garland Science.
Figure 3.9 Activation of adenylyl cyclase and formation from cAMP as second messenger.
Source: Alberts et al. (2015). Adapted with permission of Garland Science.
Table 3.3 The role of adenylyl cyclase and phospholipase C‐β in signal transduction.
| Signaling molecule | Target tissue | Main reaction |
|---|---|---|
| Adenylyl cyclase | ||
| Adrenaline | Heart | Raising heart frequency and enhancing contraction, muscles, glycogen degradation |
| Muscle | Breakdown of glycogen | |
| ACTH | Adrenal gland (cortex) | Secretion of cortisone |
| ACTH, adrenaline | Fat tissue | Breakdown of triglycerides |
| Glucagon | Liver | Glycogen degradation, increase of blood glucose levels |
| Parathormone | Bone | Bone resorption |
| Vasopressin | Kidney | Water resorption |
| Luteinizing hormone | Ovary | Progesterone secretion |
|
Thyroid‐stimulating | ||