No abstract

The RNA world hypothesis suggests that chemical networks consisting of functional RNA molecules could have constructed a primitive life-like system leading a first living system. The chemical evolution scenario of RNA molecules should be consistent with the Hadean Earth environment. We have demonstrated the importance of the environment at both high temperature and high pressure, using different types of hydrothermal flow reactor systems and high-pressure equipment. In the present study, we have attempted to develop an alternative easy-to-implement method for high-pressure measurements and demonstrate that the system is applicable as an efficient research tool for high-pressure experiments at pressures up to 30 MPa. We demonstrate the usefulness of the system by detecting the high-pressure influence for the self-cleavage of avocado hammerhead ribozyme (ASBVd(−):HHR) at 45–65 °C. A kinetic analysis of the high-pressure behavior of ASBVd(−):HHR shows that the ribozyme is active at 30 MPa and its activity is sensitive to pressures between 0.1–30 MPa. The surprising finding that such a short ribozyme is effective for self-cleavage at a high pressure suggests the importance of pressure as a factor for selection of adaptable RNA molecules towards an RNA-based life-like system in the Hadean Earth environment deep in the ocean.

ABSTRACT-The effects of SM-9018, a potential atypical neuroleptic, on monoamine metabolism were studied in rats. SM-9018 dose-dependently increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the cerebral cortex and striatum without affecting the levels of 5-HT, norepinephrine and their metabolites. This action persisted for 8 hr with a maximum effect at 1-2 hr. The SM-9018-induced increase of dopamine (DA) turnover, as indexed by HVA/DA and DOPAC/DA ratios, was comparable in the cerebral cortex and striatum, whereas the typical neuroleptic haloperidol preferential ly enhanced the striatal DA turnover. These findings suggest that SM-9018, unlike haloperidol, increases DA turnover to a similar extent both in the cerebral cortex and striatum.

In a previous study, we have showed that the elongation of an alanine oligopeptide [L-alanyl-L-alanyl-L-alanyl-L-alanine ((Ala))] to higher oligopeptides is enhanced by calcite and dolomite at 275°C, using a mineral-mediated hydrothermal flow reactor system. However, a problem during the use of hydrothermal flow reactor system was that some of the minerals, such as clay, could not be tested due to their clogging in the reactor. In this article, we attempted to analyze the scope of enhancement for the formation of L-alanyl-L-alanyl-L-alanyl-L-alanyl-L-alanine ((Ala)) and higher oligopeptides with different minerals including clay minerals for the elongation of alanine oligopeptide at 175°C. First, carbonate minerals and some clay minerals showed an enhancement of the formation of (Ala) from (Ala). On the contrary, volcanic products showed strong inhibitory activities. According to the pH dependence on the (Ala) elongations, we confirmed that most enhancement and inhibitory activities are due to the pH influence on the elongation of (Ala). However, the enhancement of montmorillonite (Tsukinuno), sphalerite, apatite, tourmaline, calcite (Nitto Funka), and the inhibitory activities by volcanic ash (Shinmoedake), volcanic ash (Sakurajima), dickite, and pyrophillite are not simply due to the pH change in the presence of these minerals. The difference found between the previous and present studies suggests that the interaction kinetics of the aqueous phase with the mineral phase is also an important factor for the elongation of (Ala). These data imply that the environments with pH near neutral to weak alkaline and with minerals might have been useful for the accumulation of oligopeptides in hydrothermal conditions.

We examined the effects of novel tricyclic quinoxalinedione derivatives, SM-18400 ((S)-9-chloro-5-[p-aminomethyl-o-(carboxymethoxy)phenylcarbamoylmethy l]-6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-dione hydrochloride trihydrate) and its analogs (i.e., ID-17263 and ID-17332), on the N-methyl-D-aspartate (NMDA) receptor-mediated polysynaptic reflex (PSR) in the isolated spinal cord of neonatal rats in vitro. Application of SM-18400 selectively suppressed the PSR activity in a concentration-dependent manner without affecting the monosynaptic reflex (MSR). Differential suppression of the PSR was also obtained with ID-17263, ID-17332 and other known NMDA receptor glycine-binding site antagonists, 5,7-dichlorokynurenate (5,7-diClkyn) and L-689,560 (4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4 -tetrahydroquinoline). Relative potencies of the test drugs for inhibition of the PSR were as follows: SM-18400 >> L-689,560 > ID-17332 > ID-17263 > 5,7-diClkyn. In addition, the inhibitory effects of SM-18400 on PSR were markedly antagonized by simultaneous application of D-serine, an agonist for NMDA receptor glycine-binding sites. These findings suggest that SM-18400 is a potent NMDA receptor glycine-binding site antagonist and blocks the NMDA receptor-mediated synaptic neurotransmission in the spinal cord in vitro.