Unsaturated aldehydes induce CCK secretion via TRPA1 in STC-1 cells.

SCOPE: Cholecystokinin (CCK) producing cells sense luminal contents to regulate the exocrine pancreas, gastric motility, and appetite. Although long-chain fatty acids (FAs, ≥ C12) are well known to stimulate CCK secretion, the CCK-releasing activities of other aliphatic compounds, such as aldehydes (Alds) or alcohols (Alcs), have not been studied. METHODS AND RESULTS: We tested the CCK-releasing activities of various aliphatic compounds with various carbon chain lengths (C3-C13) and degrees of unsaturation in the enteroendocrine cell line STC-1. CCK released from the cell was measured using an ELISA, and intracellular calcium concentration was measured using Fura-2. Mono- and di-unsaturated Alds at 100 µM, but not saturated Alds, induced CCK secretion in STC-1 cells. Alcs and FAs failed to induce CCK secretion, regardless of carbon chain length or degree of unsaturation. Unsaturated Alds increased intracellular calcium concentration, but saturated Alds, Alcs, and FAs did not. Intracellular calcium mobilization and CCK secretion induced by unsaturated Alds was abolished in the absence of extracellular calcium. In addition, the inhibition of the transient receptor potential ankyrin 1 (TRPA1) channel suppressed unsaturated Ald-induced CCK secretion and intracellular calcium mobilization. CONCLUSION: Unsaturated Alds are potent aliphatic stimulants for CCK secretion through the activation of TRPA1.

Additional copies of CBX2 in the genomes of males of mammals lacking SRY, the Amami spiny rat (Tokudaia osimensis) and the Tokunoshima spiny rat (Tokudaia tokunoshimensis).

Tokudaia osimensis (the Amami spiny rat) and Tokudaia tokunoshimensis (the Tokunoshima spiny rat) have a sex chromosome composition of XO/XO, no Y chromosome. The mammalian sex-determining gene, SRY, is also absent in these species, which indicates that these spiny rats exhibit a novel sex-determining mechanism that is independent of SRY. To identify a candidate gene that controls this mechanism, the copy numbers and chromosomal locations of 10 genes with important functions in gonadal differentiation were determined: ATRX, CBX2 (M33), DMRT1, FGF9, NR0B1 (DAX1), NR5A1 (Ad4BP/SF1), RSPO1, SOX9, WNT4, and WT1. Multiple bands were detected for NR0B1 in Southern blot analysis, which suggested the presence of multiple copies of the gene in the genomes of these two species. CBX2 was localized to two loci in both sexes of the two species by fluorescence in situ hybridization mapping: 3q24 and 6p11.2 in T. osimensis and 10q25-q26 and 14q12-q13.1 in T. tokunoshimensis. Quantification of copy numbers in the two species by quantitative real-time PCR indicated that there were two or three more copies of CBX2 per haploid genome in males (T. osimensis, n = 3; T. tokunoshimensis, n = 2) than in females (T. osimensis, n = 4; T. tokunoshimensis, n = 2), whereas NR0B1 was present as a single copy in both. The results suggest that additional copies of CBX2 in males might be involved in a novel sex-determining mechanism in species that lack SRY.