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1 Capsaicin sensitive a erent nerves play an important role in gastric mucosal defensive mechanisms. Capsaicin stimulates a erent nerves and enhances the release of calcitonin gene-related peptide (CGRP), which seems to be the predominant neurotransmitter of spinal a erents in the rat stomach, exerting many pharmacological e ects by a direct mechanism or indirectly through second messengers such as nitric oxide (NO). 2 Lafutidine is a new type of anti-ulcer drug, possessing both an antisecretory e ect, exerted via histamine H 2 receptor blockade, and gastroprotective activities. Studies with certain antagonists or chemical dea erentation techniques suggest the gastroprotective actions of lafutidine to be mediated by capsaicin sensitive a erent nerves, but this is an assumption based on indirect techniques. In order to explain the direct relation of lafutidine to a erent nerves, we conducted the following studies.3 We determined CGRP and NO release from rat stomach and speci®c [ 3 H]-resiniferatoxin (RTX) binding to gastric vanilloid receptor subtype 1 (VR1), which binds capsaicin, using EIA, a microdialysis system and a radioreceptor assay, respectively. 4 Lafutidine enhanced both CGRP and NO release from the rat stomach induced by a submaximal dose of capsaicin, but had no e ect on speci®c [ 3 H]-RTX and capsaicin binding to VR1. 5 In conclusion, our ®ndings demonstrate that lafutidine modulates the activity of capsaicin sensitive a erent nerves in the rat stomach, which may be a key mechanism involved in its gastroprotective action.

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We examined the effects of basic fibroblast growth factor (FGF-2) on cultured lower molar tooth germ at the differentiative (bell) stage. Although FGF-2 has been detected in odontogenesis, its roles in biological activities, such as cell proliferation, differentiation and extracellular matrix mineralization are unclear. We assayed mRNA levels of the differentiation markers, dentine sialophosphoprotein (DSPP), amelogenin and alkaline phosphatase (ALP) using reverse transcription-polymerase chain reaction (RT-PCR), and histological methods. Tooth germs dissected from 17-day-old embryonic mice were cultured for 4 days with either recombinant human FGF-2 or specific antisense phosphorothioate oligodeoxynucleotide (antisense ODN) for FGF-2. Exogenous FGF-2 decreased the gene expression of differentiation markers in molars at the bell stage. Abrogation of endogenous FGF-2 by antisense ODN increased the gene expression of differentiation markers, and also significantly enhanced enamel and dentine formation. This histological change was recovered by adding exogeneous FGF-2. These findings suggest that FGF-2 at the bell stage regulates cell differentiation and matrix secretion.