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

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 approximately 30,000, has been identified as the major serum mitogen for these cells; 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 factor, fibroblast growth factor, insulin and somatomedins. 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 cells. Substance P and substance K (also known as neurokinin A or neuromedin L) are mammalian peptides belonging to the tachykinin family. Substance P has been studied extensively; it is distributed widely throughout the central and peripheral nervous system, including primary sensory neurones, and can be released in the periphery from axon collaterals of stimulated pain fibres and contribute to the inflammatory response. Substance K is a member of the tachykinin family isolated from mammalian spinal cord; Nawa et al. 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 fibroblasts, and that this stimulation is inhibited by the substance P-antagonist spantide.

Physical activity modulates nerve plasticity and stimulates repair after achilles tendon rupture

“…Although this could be attributed to physical activity inhibiting new nerve ingrowth in general, this seems less likely given the number of reports showing that sensory neuropeptides increase the proliferation of fibroblasts and endothelial cells. 13,23,24 Therefore, we hypothesize that high physical activity causes an earlier both in-growth and disappearance of nerve fibers from the tendon proper. The disappearance of nerve fibers already at 4 weeks would seem to reflect a more mature stage of healing compared to that noted in freely moving rats in the longitudinal study, in which the disappearance did not occur until much later, that is, between week 8 to 16 (Fig.…”

“…11 The two sensory neuropeptides analyzed, that is, substance P (SP) and calcitonine gene related peptide (CGRP), have previously been reported to promote angiogenesis and tissue regeneration, 12,13,15,16,23,26 partly by stimulating proliferation of endothelial cells and fibroblasts. 12,13,23,24 Given that neuropeptides mediate trophic effects, it might prove that the positive effects seen after mechanical stimulation, that is, early mobilization and exercise after tendon injury, is mediated to some extent by the peripheral nervous system.…”

Tissue distribution and quantitation of the mRNAs for three rat tachykinin receptors

“…Tachykinin peptides may also act as growth factors [23] or may contribute to local neurogenic inflammation [24]. Since a variety of these biological activities are elicited by all three tachykinin peptides, it is often thought simply that the three peptides all participate in evoking a variety of physiological responses in the CNS and peripheral tissues.…”

NK1‐receptors mediate the proliferative response of human fibroblasts to tachykinins

“…Strong pharmacological and physiological evidence indicates that TKs release in the periphery takes place during the well-known phenomenon of 'neurogenic inflammation' (Lembeck & Holzer, 1979; see Chahl, 1988 andHolzer, 1988 for review). Nilsson et al (1985) reported that TKs exert a potent stimulant action on proliferation of human skin fibroblasts and, on this basis, a possible role of endogenous TKs on wound healing was suggested (see also Maggi et al, 1987a;Kjartansson et al, 1987).…”

“…SP, NKA and NKB stimulate preferentially NK,-, NK2-and NK3-receptors, respectively . Nilsson et al (1985) . Recently the task of charactert Author for correspondence.…”