Sex-dependent action of prenatal fractionated X-irradiation in the mouse. Biochemical findings

Summary X-Irradiation of pregnant NMRI-mice on gestational days 11–13 with 3×1.05 Gy increased postnatal mortality of the female offspring only. Weights, protein content and acetylcholinesterase, as well as Na, K-ATPase activities in the brains of all treated offspring, were changed. There were, however, no differences between females and males with respect to these parameters.We gratefully acknowledge the assistance of Miss C. Gutmann.     

Topographical distribution of ATP in rat brain.

Studies on the distribution of ATP in microdissected segments of the rat brain indicate that the nucleotide is concentrated in gray matter, and especially in the thalamus, hippocampus, entorhinal cortex and sensorimotor cortex. These distribution studies in conjunction with previous neuropharmacological studies, support the concept that adenine nucleotides may function as intercellular mediators in various regions of the brain.     

Effect of cyproheptadine on the octopamine-induced responses in the mammalian central nervous system

Summary Extracellular recordings have been made from rat thalamic neurones anaesthetized with urethane, 1.5–2 g/kg i.p. Iontophoretically applied octopamine excited certain thalamic neurones in the ventral basal complex while inhibiting others. Both effects were reversibly antagonized by iontophoretically applied cyproheptadine without affecting responses to noradrenaline and dopamine.Acknowledgment. We are grateful to Merck, Sharp and Dohme for a gift of cyproheptadine HCl.     

Proton motive force mediates a reorientation of the cytosolic domains of the multidrug transporter LmrP

LmrP from Lactococcus lactis is a 45-kDa membrane protein that confers resistance to a wide variety of lipophilic compounds by acting as a proton motive force-driven efflux pump. This study shows that both the proton motive force and ligand interaction alter the accessibility of cytosolic tryptophan residues to a hydrophilic quencher. The proton motive force mediates an increase of LmrP accessibility toward the external medium and results in higher drug binding. Residues Asp128 and Asp68, from cytosolic loops, are involved in the proton motive force-mediated accessibility change. Ligand binding does not modify the protein accessibility, but the proton motive force-mediated restructuring is prerequisite for a subsequent accessibility change mediated by ligand binding. Asp142 cooperates with other membrane-embedded carboxylic residues to promote a conformational change that increases LmrP accessibility toward the hydrophilic quencher. This drug binding-mediated reorganization may be related to the transition between the high- and low-affinity drug-binding sites and is crucial for drug release in the extracellular medium.     

Comparison of the inhibition of avian and mammalian bone alkaline phosphatases by levamisole and compound R8231

Summary Alkaline phosphatases from mammalian bone are inhibited much more than chick bone alkaline phosphatase by levamisole and compound R8231. Doses of R8231 (10^–4 to 10^–5 M) that almost completely inhibit mammalian alkaline phosphatases do not inhibit the growth of embryonic rat femurs in vitro. R8231 should be an excellent biological probe for the function of alkaline phosphatase in bone metabolism.Acknowledgments. This work has been supported by funds from the Medical Research Council.     

The optical rotatory dispersion curves oftrans-decalones and their polycyclic analogues

Zusammenfassung Der Einfluss von Methylsubstituenten, sowie von zusätzlich anellierten Ringen auf die Amplitude der Rotationsdispersionskurve vontrans-Dekalon (1) undtrans-Dekalon (2) wird durch Analyse eines umfangreichen Tatsachenmaterials ermittelt. Die in tabellarischer Form zusammengestellten, für den jeweiligen Substitutionstyp charakteristischen Beiträge verhalten sich in erster Näherung additiv und können deshalb zur Überprüfung von Strukturen, Konfigurationen und Konstellationen herangezogen werden.

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Paper IX of the seriesOptical Rotatory Dispersion. For Paper VIII, seeJ. Hrbek jr., J. P. Jennings, W. Klyne, andF. antavý, Coll. Czech. Chem. Comm.,29, in press (1964).