Semipermeable lipid bilayers exhibit diastereoselectivity favoring ribose.

Nutrient uptake by a primitive cell would have been limited by the permeability characteristics of its membrane. We measured the permeabilities of model protocellular membranes to water, five of the six pentoses, and selected aldohexoses, ketohexoses, and three to six carbon alditols by following volume changes of vesicles after the addition of solute to the external medium. Solute hydrophobicities correlated poorly with permeability coefficients within one structural class of compounds. The permeability coefficients of diastereomeric sugars differed by as much as a factor of 10, with ribose being the most permeable aldopentose. Flexible alditols and sugars, sugars biased toward or restricted to furanose forms, and sugars having anomers with hydrophobic faces permeated more quickly than compounds lacking these features. Among the aldopentoses, only ribose possesses all of these properties. Ribose permeated both fatty acid and phospholipid membranes more rapidly than the other aldopentoses or hexoses. The enhanced permeability conferred by the unique conformational preferences of ribose would have allowed faster assimilation of ribose by primitive cells as they passively absorbed materials from the environment. The kinetic advantage of ribose over the other aldopentoses in crossing membranes may therefore have been one factor that facilitated the emergence of the RNA world.

Interaction between the serotoninergic and dopaminergic systems in d-fenfluramine-induced activation of c-fos and jun B genes in rat striatal neurons.

To test for the relative contributions of the dopaminergic and serotoninergic systems in the striatum to the effects of d-fenfluramine, an indirect serotonin receptor agonist, we assessed the expression of Fos/Jun proteins induced by d-fenfluramine given alone or in the presence of dopaminergic or serotoninergic agents. To determine the neuronal targets of d-fenfluramine in the striatum, we identified the phenotypes of striatal neurons in which d-fenfluramine induced Fos expression. Our results demonstrated that d-fenfluramine evokes nuclear expression of Fos/Jun B proteins in the striatum, and that the Fos expression was dose-dependent and accompanied by transient induction of c-fos mRNA. Fos expression was blocked by p-chloroamphetamine, a serotoninergic neurotoxin. Pretreatment with SCH 23390, a D1-dopamine receptor antagonist, led to a marked decrease in Fos/Jun B expression in the caudoputamen, but not in the cortex, whereas pretreatment with methiothepin, a nonselective serotonin 5-HT1 receptor antagonist, blocked Fos expression completely in the cortex and only partially in the caudoputamen. The expression of Fos/Jun B in the striatum occurred mainly in dynorphin-containing neurons and in a subpopulation of striatal interneurons that exhibited NADPH-diaphorase activity. Most of the enkephalin-containing neurons of the striatum did not show Fos/Jun B staining. These results suggest that the mechanism by which d-fenfluramine induces c-fos and jun B expression in the rat caudoputamen depends at least in part on activation of the dopaminergic system by serotonin.