Viously demonstrated that sea lamprey (Petromyzon marinus), zebrafish, and AfricanKrasowski et al. BMC Biochemistry , ON123300 biological activity 15150104?dopt=Abstract” title=View Abstract(s)”>PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/15150104?dopt=Abstract : http:biomedcentral-Page ofFigure Representative bile salts and their structures. All bile salts are derived from cholesterol (topmost structure), illustrated together with the carbon atoms numbered plus the steroid rings labelled A, B, C, and D. Jawless fish, lobe-finned fish, and also a restricted quantity of actinopterygian fish use a bile alcohols for instance a-cyprinol–sulfate which have an overall planar and extended structure with the steroid rings (see representation of A, B, and C rings around the right side). Most actinopterygian fish (like medaka and Tetraodon nigrivirdis) use b bile acids which have an all round bent structure from the steroid rings. Among the list of two most common main salts in mammals is chenodeoxycholic acid (CDCA), the stem C bile acid which has the fundamental a,a-dihydroxylation pattern. Lithocholic acid is one of the smallest naturally occurring bile acids and benefits from bacterial enzyme-mediated deconjugation and dehydroxylation of principal bile acids. The sodium and calcium salts of lithocholic acid have very low solubility at body temperature. On top of that, lithocholic acid is toxic in humans and also other mammals.Krasowski et al. BMC Biochemistry , : http:biomedcentral-Page ofclawed frog FXRs are activated by bile alcoholsSea lamprey and zebrafish FXRs are selective for planar a bile alcohols. The Xenopus FXR isoform was activated by a- and b-bile alcohols (paralleling the complicated bile salt profile of this amphibian) but was poorly activated by bile acids ,. The vitamin D receptor (VDR; NRI) is identified to mediate the action of ,-dihydroxyvitamin D (calcitriol), a hormone whose `classic’ function would be to regulate calcium and phosphorus homeostasis. Nonetheless, VDRs are now recognized to be inved inside 
a wide range of physiological processes which includes immune technique modulation, skin development, and regulation of your metabolism of toxic compounds -. Two VDR genes have already been located in the genome of many actinopterygian fish (a most likely by-product of whole genome duplication prior to actinopterygian fish radiation) -, with VDRa and VDRb each shown to be functional within the Japanese medaka (Oryzias latipes)Mammalian VDRs are activated at low affinity by a narrow array of b-bile acids, particularly the toxic secondary bile acid LCA and its derivatives ,-. VDR activation within the intestine has been shown to upregulate the expression of enzymes (e.gCYPA) that will metabolize and lessen the toxicity of LCA -. We previously determined that the VDR from the sea lamprey (Petromyzon marinus) was insensitive to activation by a wide array of bile salts, which includes bile acids and bile alcohols with a selection of substituents. We proposed the hypothesis that activation of VDRs by bile acids is really a `derived’ trait, possibly as an adaptation to eutionary modifications in bile salt pathways and vertebrate physiology that enable for generation of toxic secondary bile acidsIn this report, we characterize the ligand selectivity of FXR, VDR, and PXR in the ABT-639 web green-spotted pufferfish (Tetraodon nigriviridis), an actinopterygian fish that synthesizes primarily the b-bile acids CA and CDCA , thereby getting a bile salt profile similar to most mammals. We also cloned and characterized VDRs from three additional non-mammalian species: medaka, African clawed frog, and chicken (Gallus gallus). In terms of key bile salts, the medaka synthesizes a mixture of b C and C bile acids ,. The Afric.Viously demonstrated that sea lamprey (Petromyzon marinus), zebrafish, and AfricanKrasowski et al. BMC Biochemistry , PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/15150104?dopt=Abstract : http:biomedcentral-Page ofFigure Representative bile salts and their structures. All bile salts are derived from cholesterol (topmost structure), illustrated together with the carbon atoms numbered as well as the steroid rings labelled A, B, C, and D. Jawless fish, lobe-finned fish, along with a limited number of actinopterygian fish use a bile alcohols including a-cyprinol–sulfate that have an all round planar and extended structure from the steroid rings (see representation of A, B, and C rings around the suitable side). Most actinopterygian fish (which includes medaka and Tetraodon nigrivirdis) use b bile acids which have an overall bent structure from the steroid rings. Among the list of two most typical key salts in mammals is chenodeoxycholic acid (CDCA), the stem C bile acid that has the basic a,a-dihydroxylation pattern. Lithocholic acid is among the smallest naturally occurring bile acids and benefits from bacterial enzyme-mediated deconjugation and dehydroxylation of main bile acids. The sodium and calcium salts of lithocholic acid have quite low solubility at body temperature. On top of that, lithocholic acid is toxic in humans along with other mammals.Krasowski et al. BMC Biochemistry , : http:biomedcentral-Page ofclawed frog FXRs are activated by bile alcoholsSea lamprey and zebrafish FXRs are selective for planar a bile alcohols. The Xenopus FXR isoform was activated by a- and b-bile alcohols (paralleling the complex bile salt profile of this amphibian) but was poorly activated by bile acids ,. The vitamin D receptor (VDR; NRI) is recognized to mediate the action of ,-dihydroxyvitamin D (calcitriol), a hormone whose `classic’ function is always to regulate calcium and phosphorus homeostasis. Nonetheless, VDRs are now recognized to be inved in a wide range of physiological processes like immune system modulation, skin development, and regulation in the metabolism of toxic compounds -. Two VDR genes happen to be identified within the genome of lots of actinopterygian fish (a likely by-product of complete genome duplication before actinopterygian fish radiation) -, with VDRa and VDRb both shown to be functional inside the Japanese medaka (Oryzias latipes)Mammalian VDRs are activated at low affinity by a narrow range of b-bile acids, especially the toxic secondary bile acid LCA and its derivatives ,-. VDR activation inside the intestine has been 
shown to upregulate the expression of enzymes (e.gCYPA) which can metabolize and decrease the toxicity of LCA -. We previously determined that the VDR in the sea lamprey (Petromyzon marinus) was insensitive to activation by a wide array of bile salts, such as bile acids and bile alcohols with a selection of substituents. We proposed the hypothesis that activation of VDRs by bile acids is usually a `derived’ trait, possibly as an adaptation to eutionary alterations in bile salt pathways and vertebrate physiology that enable for generation of toxic secondary bile acidsIn this report, we characterize the ligand selectivity of FXR, VDR, and PXR from the green-spotted pufferfish (Tetraodon nigriviridis), an actinopterygian fish that synthesizes primarily the b-bile acids CA and CDCA , thereby having a bile salt profile comparable to most mammals. We also cloned and characterized VDRs from 3 extra non-mammalian species: medaka, African clawed frog, and chicken (Gallus gallus). When it comes to main bile salts, the medaka synthesizes a mixture of b C and C bile acids ,. The Afric.