5 (PGP9.5) [74], neural cell adhesion molecule (NCAM) [75], synaptosomal-associated protein 25 (SNAP25) [76] and [77] and glutamic acid decarboxylase

67 (GAD67) [78]. Based on these studies, expression analysis of mRNA for ANG II receptors, AT1 and AT2, in taste tissues were conducted by RT-PCR and in situ hybridization. AT1 mRNAs were expressed in fungiform and circumvallate papillae in B6 mice, but not in epithelial tissue without taste buds. The expression pattern was similar to see more those of RT-PCR products for the type II taste cell marker Trpm5 and the type III taste cell marker/sour receptor candidate Pkd2L1. AT2 mRNAs were not expressed in any of these tissues. In in situ hybridization analyses, AT1 mRNAs were detected in a subset of cells in fungiform and

circumvallate papillae but not in surrounding epithelial cells. These results suggest that AT1, but not AT2, is expressed in mouse taste bud cells of both the anterior and posterior tongue, and ANG II is able to act on peripheral taste cells via AT1 [48]. By double labeled immunohistochemistry, AT1 proteins were co-expressed with an amiloride-sensitive salt taste receptor, αENaC, or a sweet taste receptor component, T1r3 (as marked by T1r3-GFP), not with a sour receptor candidate, Pkd2L1, in a subset of taste cells in both fungiform and circumvallate papillae in B6 TSA HDAC manufacturer mice. Previous studies have shown that amiloride-sensitive taste cells express ENaC subunits, but not Gα-gustducin (type II cells), or SNAP25 (type III cells) [22], [76] and [77]. No overlap in the expression of αENaC and Trpm5 is observed in fungiform or palate taste buds [23]. These results suggest that the amiloride sensitive salt and sweet taste modulations by ANG PIK-5 II may be mediated by independent cellular mechanisms in ENaC or T1r3 expressing taste cells [48]. Endocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known as orexigenic mediators that act via cannabinoid receptor 1 (CB1) in the hypothalamus and limbic forebrain to induce

appetite and stimulate food intake [79] and [80]. It is also shown that endocannabinoids enhance sweet taste sensitivity of T1r3 positive taste cells via CB1 [52]. Moreover, It is reported that CB1 is transactivated by AT1 in Chinese hamster ovary cells [81], or significant up-regulation of AT1-CB1 heteromers and enhancement of ANG II-mediated signalling as compared with control [82]. These results raised the possibility that the transactivation of CB1 by AT1 in sweet taste cells would enhance sweet taste sensitivity by administration of ANG II. To assess this possibility, the effects of ANG II on taste responses were examined using CB1-knockout (KO) mice [83]. As observed in B6 control mice, the CT nerve responses to NaCl in CB1-KO mice were significantly decreased after administration of ANG II.