BAM8-22 and its receptor MRGPRX1 may attribute to cholestatic pruritus
Autor: | Han-Joo Maeng, Babina Sanjel, Won-Sik Shim |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Keratinocytes Male medicine.medical_specialty Sensory Receptor Cells lcsh:Medicine Endogeny Molecular neuroscience Calcium in biology Article Cell Line Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cholestasis Internal medicine Chenodeoxycholic acid Ganglia Spinal medicine Animals Humans Protein Precursors lcsh:Science Receptor Cholestatic pruritus Mice Inbred ICR Multidisciplinary integumentary system Behavior Animal Chemistry Pruritus lcsh:R Enkephalins medicine.disease Peptide Fragments Proenkephalin Up-Regulation HaCaT 030104 developmental biology Endocrinology lcsh:Q Sensory processing Cattle Bile Ducts 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) |
ISSN: | 2045-2322 |
Popis: | Pruritus is an unexpected symptom observed in cholestasis and its mechanism is still unclear. Here, we show that bovine adrenal medulla (BAM) 8–22, an endogenous itch-inducing peptide, could be involved in cholestatic pruritus. It was found that bile duct ligation (BDL) mice, an obstructive cholestasis model, showed increased spontaneous scratching behaviour. Importantly, the mRNA level of proenkephalin, a precursor polypeptide of BAM8-22, was significantly increased in the skin of BDL mice. Furthermore, the mRNA level of Mrgprx1, which encodes a receptor for BAM8-22, was significantly increased in the dorsal root ganglia (DRG) of BDL mice. This was further confirmed by elevation of intracellular calcium levels upon BAM8-22 treatment in primarily-cultured DRG neurons. In addition, BDL mice showed augmented scratching behaviour by BAM8-22, indicating enhanced activity of MRGPRX1. Moreover, the skin homogenate of BDL mice induced elevation of intracellular calcium levels through MRGPRX1. Finally, among the various bile acids, chenodeoxycholic acid significantly increased proenkephalin transcription in a human keratinocyte cell line (HaCaT). In conclusion, cholestatic pruritus could be attributed in part to enhanced action of both BAM8-22 in the skin and its receptor MRGPRX1 in sensory neurons. |
Databáze: | OpenAIRE |
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