piperidines and jervine

In the adult brain, sonic hedgehog acts on cerebral microvascular endothelial cells to stabilize the blood-brain barrier. The expression of sonic hedgehog by astrocytes is altered during brain injury, and this change has been shown to affect permeability of blood-brain barrier. However, much remains unknown about the regulation of astrocytic sonic hedgehog production. Our results showed that endothelin-1 reduced sonic hedgehog mRNA expression and extracellular protein release in mouse cerebral cultured astrocytes, but had no effect in bEnd.3, a mouse brain microvascular endothelial-derived cell line. The effect of endothelin-1 on astrocyte sonic hedgehog expression was suppressed by an ET

Topics: Animals; Astrocytes; Blood-Brain Barrier; Brain Injuries, Traumatic; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Endothelin-1; Hedgehog Proteins; Male; Mice; Oligopeptides; Piperidines; Receptor, Endothelin B; Veratrum Alkaloids

All four diastereomers of the trisubstituted piperidine-alkaloids of the veratramine and jervine type were synthesized with complete stereocontrol starting from enantiopure citronellic acids. The flexible, high-yielding, and scalable route described here will facilitate convergent syntheses and give access to analogues of cyclopamine and other biologically active and diverse steroid alkaloids.

Topics: Biological Products; Catalysis; Molecular Structure; Piperidines; Stereoisomerism; Veratrum Alkaloids

High-pressure liquid chromatography was used to separate the following steroidal alkaloids: tomatidine, solanidine, solasodine, rubijervine, veratramine and jervine. The method was used to prepare crystalline solanidine from a crude mixture of aglycones obtained from Solanum chacoense, and to separate radioactive solanidine from extracts of potato plants fed with [4-C]cholesterol.

Topics: Alkaloids; Chromatography, High Pressure Liquid; Methods; Piperidines; Solanaceous Alkaloids; Spirostans; Steroids; Tomatine; Veratrum Alkaloids

Golden hamster fetuses were extremely sensitive to the teratogenic action of jervine and cyclopamine, the steroidal alkaloid tetratogens from Veratrum californicum. Cebocephaly, harelip/cleft palate, exencephaly, and a cranial bled were the common deformities produced by dosing on the seventh day of gestation. Sprague-Dawley derived albino rats were susceptible to cyclopamine but not to jervine, and at an incidence very much lower than that of hamsters. Cebocephaly and microphthalmia were the common deformities. The terata were observed as a consequence of sixth to ninth-day dosings. Single-day dosings produced no terata. Swiss Webster mice were apparently resistant to the teratogens.

Topics: Animals; Brain; Cleft Lip; Cricetinae; Female; Furans; Gestational Age; Mice; Microphthalmos; Piperidines; Pregnancy; Rats; Teratogens; Veratrum Alkaloids