Transmitter and peptide receptors: Basic principles

Receptors are signaling proteins that are responsible for converting extracellular stimuli to intracellular responses. These responses can occur on millisecond time scales or take minutes or even hours. In addition to temporal dynamics of signaling, receptors mediate signal amplification and signal processing. Signal amplification occurs by receptor activity-mediated increase in the concentration of many intracellular molecules. Signal processing occurs when a variety of intracellular events produced upon activation of the receptor lead to an appropriate response. According to the classic model of receptor activation, a specific receptor responds to one specific chemical neurotransmitter. This model is continuing to be revised since in many cases, a specific ligand is able to activate a number of distinct targets and alternatively, different ligands are able to bind and activate the same receptor. The types of endogenous ligands that stimulate receptors vary widely in their physiochemical properties ranging from amino acids (glutamate), peptides (enkephalin, neuropeptide Y), large proteins (follicle-stimulating hormone), nucleosides (adenosine), lipids (2-arachidonoylglycerol), divalent ions (calcium), or steroids (estrogen). These ligands activate four major classes of receptors: ligand-gated ion channels, G-protein-coupled receptors, enzyme-linked receptors, and nuclear hormone receptors. The structure and mechanism of action of receptors are diverse because of the diversity of ligands activating the receptor and the time scales that the signal needs to be transmitted. Approximately half of all drug targets are receptors. Therefore, an understanding of receptors is important both for basic neuroscience as well as neuropharmacology and applied biomedical sciences.