ABSTRACT
We have established an efficient synthesis of mimics of beta-galactosylceramide (beta-GalCer) increasing a beta-glucocerebrosidase (beta-GlcCer'ase) activity that associates with the skin barrier function. Among the synthetic beta-GalCer analogues (6a-6e) described herein, compound 6e exhibited a potent effect on the activation of beta-GlcCer'ase function in vitro and reduced the transepidermal water loss (TEWL) level in a UVB-induced barrier disrupted mice model. These findings indicated that compound 6e could be useful for cosmetics and medicines to improve skin barrier function.
Subject(s)
Biomimetic Materials/chemical synthesis , Biomimetic Materials/pharmacology , Galactosylceramides/chemical synthesis , Galactosylceramides/pharmacology , Glucosylceramidase/metabolism , Keratinocytes/drug effects , Animals , Cells, Cultured , Drug Design , Enzyme Activation/drug effects , Epidermis/drug effects , Epidermis/metabolism , Epidermis/radiation effects , Humans , Keratinocytes/enzymology , Keratinocytes/radiation effects , Mice , Structure-Activity Relationship , Ultraviolet Rays , Water Loss, Insensible/drug effects , Water Loss, Insensible/radiation effectsABSTRACT
Ghrelin is an acylated peptide that stimulates food intake and the secretion of growth hormone. While ghrelin is predominantly synthesized in a subset of endocrine cells in the oxyntic gland of the human and rat stomach, the mechanism regulating ghrelin secretion remains unknown. Somatostatin, a peptide produced in the gastric oxyntic mucosa, is known to suppress secretion of several gastrointestinal peptides in a paracrine fashion. By double immunohistochemistry, we demonstrated that somatostatin-immunoreactive cells contact ghrelin-immunoreactive cells. A single intravenous injection of somatostatin reduced the systemic plasma concentration of ghrelin in rats. Continuous infusion of somatostatin into the gastric artery of the vascularly perfused rat stomach suppressed ghrelin secretion in both dose- and time-dependent manner. These findings indicate that ghrelin secretion from the stomach is regulated by gastric somatostatin.
