Effect of substance P and protein kinase inhibitors on β-amyloid peptide-induced proliferation of cultured brain cells

The present study investigated the effect of substance P (SP) and protein kinase inhibitors (H7 and HA1004) on β-amyloid peptide-induced proliferation of neonatal rat brain cells in primary cultures. The β-amyloid peptide_1–28 (designated as βAP28), at nanomolar concentrations (10⁻⁹ M), significantly (P 0.05) increased the proliferation of brain cells (presumably non-neuronal) as measured by [³H]thymidine uptake into DNA (mitogenesis). The effect was dependent on time of cultured, concentration of βAP28, and presence of fetal calf serum. The supplementation of SP into cell cultures at time zero reversed the proliferative response of βAP28. Moreover, the βAP28-induced proliferation was inhibited by protein kinase inhibitor H7, but not by HA1004. Since H7 is a selective protein kinase C (PKC) inhibitor and SP action involves PKC, we conclude that βAP28 induces normal brain cell proliferation through PKC pathway of cell signaling.