Liposomal VIP potentiates DNA synthesis in cultured oral keratinocytes

The purpose of this study was to determine whether association of vasoactive intestinal peptide with sterically stabilized liposomes (VIP on SSL) amplifies DNA synthesis evoked by the peptide in cultured chemically transformed hamster oral keratinocytes (HCPC-1) and, if so, whether this response in mediated, in part, by SSL-induced inactivation of neutral endopeptidase 24.11 (NEP; EC 3.4.24.11) and angiotensin I-converting enzyme (ACE; EC 3.4.15.1), two ectoenzymes that modulate HCPC-1 cell growth, in these cells. We found that VIP (10 −9–10 −6 M) alone elicited a modest, albeit significant, concentration-dependent increase in DNA synthesis in HCPC-1 cells that was maximal after 48–72-h incubation ( p < 0.05). VIP on SSL potentiated DNA synthesis in these cells relative to VIP alone. The magnitude of VIP on SSL-induced responses was 1.2–1.6-fold higher than that of VIP alone with maximal effects observed at 10 −9 M and 10 −6 M after 72- and 48-h incubation, respectively. Empty SSL had no significant effects on DNA synthesis. Empty SSL and VIP on SSL had no significant effects on NEP 24.11 and ACE activity in HCPC-1 cells. Collectively, these data indicate that association of VIP with SSL potentiates DNA synthesis in cultured oral keratinocytes relative to VIP alone and that this response is not related to non-specific effects of SSL.