ABSTRACT
Division of Gastroenterology-Hepatology, Department of Medicine, University of Iowa, Iowa City, IA 52242, USA
Substance P (SP) is an 11 amino acid molecule derived from the preprotachykinin A gene. It is a product of both nerves and leukocytes. SP-containing nerves are in thymus, bone marrow, spleen and many other organs. SP binds with high affinity to a G-proteincoupled, seven transmembrane receptor called NK1, which is its natural ligand. NK1 receptors may use one of several distinct intracellular signalling pathways depending on influences from the external environment. NK1 receptors are displayed throughout the body on vascular endothelial cells, epithelial cells, smooth muscle cells, neurons, lymphocytes, macrophages and other cell types. The NK 1 receptor and SP expression are subject to immunoregulation. SP and its receptor clearly have immune functions. They are important for mediating a process called neurogenic inflammation. They also have critical roles in several infectious, toxin and antigen-induced models of inflammation. In the thymus and bone marrow, SP may have ongoing steady-state functions. There are various reported effects of SP on cells of the immune system. Differences exist among rodents, guinea pigs and humans. Some of the biological activities attributed to SP occur only at high SP concentrations suggesting signalling pathways independent of NK1 receptors. The physiological significance of most of these observations has not yet been tested in context of inflammation or disease. There are several nonpeptide NK1 receptor antagonists under clinical evaluation, which may ultimately lend insight into the critical physiological roles of SP in humans.
