Stimulation of connective tissue cell growth by substance P and substance K

Publisher Website
Google Scholar
Abstract
Connective tissue cells proliferate actively when cultured in the presence of serum. Platelet-derived growth factor (PDGF), a basic protein of relative molecular mass ∼ 30,000, has been identified as the major serum mitogen for these cells1; its main physiological/pathophysiological role may be to initiate wound healing in connection with tissue injury. However, growth of cultured cells is also influenced by several other factors, including epidermal growth factor2, fibroblast growth factor3, insulin and somatomedins4. Furthermore, Rozengurt and Sinnett-Smith recently showed that bombesin, a neuroendocrine peptide isolated from frog skin, stimulates DNA synthesis and cell division in cultures of a specific subtype of 3T3 cells5. Substance P and substance K (also known as neurokinin A or neuromedin L) are mammalian peptides belonging to the tachykinin family6. Substance P has been studied extensively; it is distributed widely throughout the central and peripheral nervous system7, including primary sensory neurones8–10, and can be released in the periphery from axon collaterals of stimulated pain fibres11,12 and contribute to the inflammatory response13. Substance K is a member of the tachykinin family isolated from mammalian spinal cord14,15; Nawa et al.16 determined the primary structure of two types of substance P precursors, one of which contained a sequence homologous to substance K, as well as the sequence of substance P. We report here that substance P and substance K stimulate DNA synthesis in cultured arterial smooth muscle cells and human skin fibro-blasts, and that this stimulation is inhibited by the substance P-antagonist spantide17.