Coupling between inositol phosphate formation and DNA synthesis in smooth muscle cells stimulated with neurokinin A
✍ Scribed by Anna Hultgårdh-Nilsson; Jan Nilsson; Bror Jonzon; Cari-Johan Dalsgaard
- Publisher
- John Wiley and Sons
- Year
- 1988
- Tongue
- English
- Weight
- 538 KB
- Volume
- 137
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
The two mammalian neuropeptides substance P (SP) and neurokinin A (NKA) have been demonstrated to stimulate DNA synthesis in connective tissue cells, suggesting that peripheral neurons may play a role in development and tissue regeneration. In this study we have tried to identify intracellular messengers required for SP-and NKA-induced DNA synthesis. SP and NKA, as well as platelet-derived growth factor (PDGF) stimulated formation of inositol phosphates in smooth muscle cells (SMC), whereas no effect on inositol phosphates formation occurred in response to nonmitogenic neuropeptides. Pretreatment of the cells with pertussis toxin markedly decreased DNA synthesis induced by NKA. This toxin inhibits formation of inositol phosphates by acting o n a regulatory G-protein. Calcium and calmodulin antagonists also inhibited NKA-induced DNA synthesis. These results imply that the mitogenic signal(s) produced by activated neuropeptide receptors involves formation of inositol phosphate and activation of a calciumlcalmodulin dependent process. We further report that other neuropeptides occurring in peripheral neurons, i.e., vasoactive intestinal polypeptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, or cholecystokinin, are without growthstimulatory effect on cultured SMC.
The recent finding that neuropeptides produced by peripheral neurons can stimulate DNA synthesis in connective tissue cells (Nilsson et al., 1985a) suggests a role for peripheral neurons in wound healing, regeneration, and development. Further evidence for a role of neuropeptides in the control of cell proliferation is the observation that neuroendocrine tumor cells produce neuropeptides that enhance the growth of these cells in a n autocrine manner (Cuttitta et al., 1985). Furthermore, the two mammalian tachykinins, substance P (SP) and neurokinin A (NKA), stimulate the rate of DNA synthe-