Liposomal VIP potentiates DNA synthesis in cultured oral keratinocytes

The purpose of this study was to determine whether association of vasoactiv ity: intestinal peptide with sterically stabilized liposomes (VIP on SSL) a mplifies DNA synthesis evoked by the peptide in cultured chemically transfo rmed 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. W e found that VIP (10(-9)-10(-6) M) alone elicited a modest, albeit signific ant, 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 DN A synthesis in these cells relative to VIP alone. The magnitude of VIP on S SL induced responses was 1.2-1.6-fold higher than that of VIP alone with ma ximal effects observed at 10(-9) and 10(-6) M after 72- and 48-h incubation , respectively. Empty SSL had no significant effects on DNA synthesis. Empt y SSL and VIP on SSL had no significant effects on NEP 24.11 and ACE activi ty in HCPC-1 cells. Collectively, these data indicate that association of V IP with SSL potentiates DNA synthesis in cultured oral keratinocytes relati ve to VIP alone and that this response is not related to non-specific effec ts of SSL. (C) 2001 Elsevier Science Inc. All rights reserved.