Title:Molecular Recognition of Tachykinin Receptor Selective Agonists: Insights from Structural Studies
Volume: 13
Issue: 14
Author(s): Anjali Ganjiwale and Sudha M. Cowsik
Affiliation:
Keywords:
Neurokinin receptor, NK1, NK2 and NK3 receptors, Structure activity relationship, Tachykinin.
Abstract: This Review deals essentially with the elucidation of structural features of Tachykinin family of neuropeptides,
which are known to interact through three distinct GPCR subtypes, namely NK1 (Neurokinin 1), NK2 (Neurokinin 2) and
NK3 (Neurokinin 3) receptors. In mammals, Tachykinins have been shown to elicit a wide array of activities such as
powerful vasodilatation, hypertensive action and stimulation of extravascular smooth muscle and are known to be
involved in a variety of clinical conditions including chronic pain, Parkinson’s disease, Alzheimer’s disease, depression,
rheumatoid arthritis, irritable bowel syndrome and asthma. This broad spectrum of action of Tachykinins is attributed to
the lack of selectivity of tachykinins to their receptors. All tachykinins interact with all the three-receptor subtypes with
SP preferring NK1, NKA preferring NK2 and NKB preferring NK3. This lack of specificity can be accounted for by the
conformational flexibility of these short, linear peptides. Hence, identification of structural features of the agonists
important for receptor binding and biological activity is of great significance in unraveling the molecular mechanisms
involved in tachykinin receptor activation and also in rational design of novel therapeutic agents. Understanding structure
of the ligand-receptor complex and analysis of topography of the binding pocket of the tachykinin receptor is also crucial
in rational design of drugs.
