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Coupling between inositol phosphate formation and DNA synthesis in smooth muscle cells stimulated with neurokinin A
Author(s) -
HultgårdhNilsson Anna,
Nilsson Jan,
Jonzon Bror,
Dalsgaard CariJohan
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041370117
Subject(s) - inositol phosphate , neurokinin a , inositol , second messenger system , pertussis toxin , neuropeptide , dna synthesis , inositol trisphosphate , calmodulin , somatostatin , biology , vasoactive intestinal peptide , medicine , cholecystokinin , microbiology and biotechnology , endocrinology , receptor , intracellular , biochemistry , signal transduction , g protein , substance p , in vitro , enzyme
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 on 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 calcium/calmodulin 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 growth‐stimulatory effect on cultured SMC.