Previously, we showed that
5-norbornene-2,2-dimethanol (5-NBene-2,2-DM) is an effective inducer of melanogenesis in cultured cells and guinea-pig skin [Brown et al. (1998) J. Invest. Dermatol., 110:428-437]. This study shows that 2,3-cis/exo-pinanediol (2,3-cs/ex-PinD) is a more effective inducer of melanogenesis than
5-NBene-2,2-DM in S91 mouse
melanoma cells. Furthermore, 2,3-cs/ex-PinD appears to penetrate guinea-pig skin better than
5-NBene-2,2-DM and to induce higher levels of pigmentation. Both
5-NBene-2,2-DM and 2,3-cs/ex-PinD induce synthesis of
nitric oxide (NO) in S91 cells, and the melanogenic activity of both compounds is reduced by inhibitors of the NO/cyclic
guanosine monophosphate (cGMP)/
protein kinase(PK) G signaling pathway, but not by inhibitors of the PKC or PKA pathways. Thus, these bicyclic
monoterpene diols appear to induce melanogenesis by the same pathway in S91 cells as that shown previously for ultraviolet radiation in melanocytes (Romero-Graillet et al. (1996) J. Biol. Chem., 271:28052-28056). These compounds also induce NO synthesis, neurite outgrowth, and
tyrosine hydroxylase activity in PC12
pheochromocytoma cells. Neurite outgrowth in PC12 cells is blocked by the
guanylate cyclase inhibitor,
LY83583 (6-anilino-2,8-quinolinequinone), indicating that, similar to S91 cells, the induction of morphological differentiation of PC12 cells by bicyclic
monoterpene diols is regulated by a cGMP-dependent pathway.