Biomaterial Database

Nonpeptide ligands for peptidergic G protein-coupled receptors. 2010

Timothy G Geary

Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, QC, Canada. timothy.g.geary@mcgill.ca

Neuropeptides play essential roles in many physiological systems in vertebrates and invertebrates. Peptides per se are difficult to use as therapeutic agents, as they are generally very unstable in biological fluid environments and cross biological membranes poorly. Recognition that nonpeptide ligands for peptide receptors have clinical utility came from the discovery that opiates (such as morphine) act by binding to G protein-coupled receptors (GPCRs) for which the endogenous ligands are a family of neuropeptides (enkephalins and endorphins). Basic research has revealed a very large number of distinct neuropeptides that influence virtually every aspect of mammalian physiology and considerable effort has been expended in the pursuit of new drugs that act through peptidergic signaling systems. Although useful drugs have been found to affect various aspects ofneuropeptide biology, most work has been devoted to the discovery of nonpeptide ligands that act as agonists or antagonists at peptidergic GPCRs. Similar opportunities are apparent for the discovery of nonpeptide ligands that act on invertebrate GPCRs. A consideration of the knowledge gained from the process as conducted for mammalian peptidergic systems can inform and illuminate promising strategies for the discovery of new drugs for the treatment and control of pests and parasites.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D009479	Neuropeptides	Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.	Neuropeptide
D011955	Receptors, Drug	Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.	Drug Receptors,Drug Receptor,Receptor, Drug
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D043562	Receptors, G-Protein-Coupled	The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.	G Protein Coupled Receptor,G-Protein-Coupled Receptor,G-Protein-Coupled Receptors,G Protein Coupled Receptors,Receptor, G-Protein-Coupled,Receptors, G Protein Coupled
D055808	Drug Discovery	The process of finding chemicals for potential therapeutic use.	Drug Prospecting,Discovery, Drug,Prospecting, Drug
D018000	Receptors, Peptide	Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells.	Peptide Hormone Receptors,Peptide Receptors,Peptide Hormone Receptor,Peptide Receptor,Receptors, Peptide Hormones,Receptors, Peptides,Hormone Receptor, Peptide,Hormone Receptors, Peptide,Hormones Receptors, Peptide,Peptide Hormones Receptors,Peptides Receptors,Receptor, Peptide,Receptor, Peptide Hormone,Receptors, Peptide Hormone