Substance P and immunoregulation

Peptides released from peripheral nerve endings in mammals, including the tachykinin substance P (SP) and vasoactive intestinal polypeptide (VIP), are potent mediators of smooth muscle and vascular functions. Significant neurophysiological activities of SP and VIP include the transmission of nociceptive and interneuron excitatory signals, respectively. SP has been shown to modulate distinct immediate hypersensitivity responses by stimulating the generation of arachidonic acid-derived mediators from mucosal mast cells but not basophils. Functions of mononuclear and polymorphonuclear leukocytes that characterize the inflammatory response and that are altered by SP include chemotaxis, lysosomal enzyme release, and phagocytic activities. The effects of SP on cell-mediated immunity are largely stimulatory, in that synthesis of DNA, protein, and immunoglobulin by mature T and B lymphocytes, respectively, is significantly enhanced at nanomolar concentrations of the neuropeptide. Functionally relevant receptors for SP on T lymphocytes have been demonstrated by cell sorter and radioligand-binding techniques, and the lymphocyte membrane proteins that comprise the SP receptor are currently being isolated and purified to homogeneity. The characterization of the structure of the SP lymphocyte receptor and identification of the receptor gene will permit detailed analyses of the molecular interactions between the immune and nervous systems.