Although T-type Ca 21 channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca V 3. to be important in pain perception, the understanding of their function is still at an early stage. Three subtypes of T-type channel have been cloned, namely, Ca V 3.1 (a 1G ), Ca V 3.2 (a 1H ) and Ca V 3.3 (a 1I ) (Cribbs et al. 1998(Cribbs et al. , 2000Gomora et al. 2002;Lee et al. 1999;Zhuang et al. 2000). Gene expression analysis demonstrated that the Ca V 3.2 subtype is predominantly found at sites essential for pain transmission, such as medium-and small-sized sensory neurons of the DRG and the superficial laminae of the dorsal horn (Talley et al. 1999). This expression pattern for Ca V 3.2 indicates that this subtype may be important for peripheral pain perception. Although Bourinet et al. recently showed reduced mechanical nociception in healthy or mononeuropathic rats following antisense-mediated knockdown of Ca V 3.2 , further exploration of the role of this channel in various pain modalities is still needed to fully validating it as a target for analgesic drug development. In the present study, we therefore investigated the roles of the Ca V 3.2 subtype in the perception of various noxious signals as well as mechanical noxious stimuli. Our results revealed that the Ca V 3.2 subtype of T-type Ca 2þ channels † † Two authors equally contributed to this work. ‡ ‡
A novel 28 kDa cysteine protease (Cs28CF) secreted by the hepatobiliary trematode, Clonorchis sinensis was identified. The protease was purified from the excretory-secretory products (ESP) of the adult worm using DEAE-ion exchange and Arginine-Sepharose 4B chromatography. It showed a high activity between pH 6.5 and 7.5 in a dithiothreitol (DTT)-dependent manner. Inhibitors specific to cysteine proteases down-regulated the activity. Addition of Cs28CF to monkey cholangiocyte cultures resulted in approximately 95% cell death after 7 days. The full-length cDNA (1078 bp) encoded a single peptide of 328 amino acids (aa) with an N-terminal hydrophobic sequence, an ERFNAQ motif in the propeptide and a mature domain. Expression of mRNA transcripts of Cs28CF was observed in both the metacercaria and adult stages. Bacterially expressed recombinant protein exhibited a specific antibody reaction with clonorchiasis sera. Deduced aa exhibited 52-76% sequence identity with the cathepsin F analogues from other organisms. A novel E/DXGTA motif was recognized in the propeptide region. Phylogenetic analysis of 63 papain family members revealed that the trematode cysteine proteases formed 2 major clades of cathepsins F and L. The trematode cysteine proteases classified as cathepsin F shared higher homology among themselves than those classified as cathepsin L. Cathepsin F is phylogenetically conserved in the trematode parasites as well as in mammals.
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