Takumi Sakai

Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign prostatic hyperplasia may be due, in part, to the blockade of the 5-HT(2A) and 5-HT(2B) receptors in the bladder.

Analysis of the expression of intercellular adhesion molecule-1 in cells of the human bronchial epithelial cell line NCI-H292

The mechanism of the expression of intercellular adhesion molecule-1 (ICAM-1) on epithelial cells was analyzed using NCI-H292 cells, a human bronchial epithelial cell line. Treatment with interferon-gamma (100 U/ml) or the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2 nM) induced ICAM-1 expression. The interferon-gamma-induced ICAM-1 expression was reduced by the tyrosine kinase inhibitor genistein (4,5,7-trihydroxyisoflavone) (37 to 185 microM), but not by the protein kinase C inhibitor Ro 31-8425 ((3-[8-(aminomethyl)-6,7,8,9-tetrahydropyrido [1.2-a]indol-10-yl]-4-(1-methyl-1 H-pyrrole-2,3-dione) (10 microM). The TPA-induced ICAM-1 expression was reduced by the protein kinase C inhibitor Ro 31-8425 (1 to 10 microM), but not by the tyrosine kinase inhibitor genistein (185 microM). The protein kinase A inhibitor H-89 (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide) did not affect the ICAM-1 expression induced by interferon-gamma or TPA. Pyrrolidine dithiocarbamate (1-pyrrolidinecarbodithioic acid) (100 microM), an inhibitor of nuclear factor kappaB (NF-kappaB) activation. enhanced the ICAM-1 expression induced by interferon-y, but reduced that induced by TPA. The changes in ICAM-1 expression on the cell surface were correlated with the changes in ICAM-1 mRNA levels. Combined treatment with interferon-gamma and TPA induced more than additive ICAM-1 expression. These findings suggest that interferon-gamma induces ICAM-1 expression by a tyrosine kinase-dependent mechanism, but that TPA induces it by a protein kinase C- and NF-kappaB-dependent mechanism.

Luminescence and scintillation properties of Tl- and In-doped CsCl crystals

The luminescence and scintillation properties of Tl- and Ce-doped Cs2HfCl6 crystals were investigated by photoluminescence and radioluminescence spectroscopy. In the photoluminescence spectra, emission bands of the activators were observed at 500 nm for Tl-doped Cs2HfCl6, and at 340 and 380 nm for Ce-doped Cs2HfCl6. The radioluminescence bands were observed at 405 and 430 nm for Tl- and Ce-doped Cs2HfCl6, respectively. Scintillation decay time constants for the Tl- and Ce-doped Cs2HfCl6 were smaller than those for the corresponding undoped crystals. Scintillation light yields for Tl- and Ce-doped Cs2HfCl6 were estimated to be 23,700 and 15,700 photons/MeV, respectively.