Chemistry of odor stimuli

The present state of the molecular basis of olfaction is shown. With the aid of various examples the regioselectivity of odor sensation is proven. The main part of the experimentation concerns the stereocontrolled process of odor release.     

Pharmacological versus binding analysis of receptor systems: How do they interplay? Myometrial cell receptors for oxytocin as a paradigm

Summary Binding studies in various biological systems frequently indicate the presence of several binding sites for a biologically active ligand. They differ in their affinity for the ligand in question, binding capacity, and Hill coefficient, which suggests differences in the mechanisms of the binding site-ligand interactions. Identification of the true receptors (sites initiating a cellular response) appears to be difficult. Three clusters of binding sites for oxytocin were found on rat myometrial cells. The oxytocin receptor seems to be linked to the medium-affinity site; the cooperation between the high-and medium-affinity sites in eliciting the uterotonic response seems likely, but lacks experimental proof. Dose-response analysis in partially irreversibly inhibited uterus preparations, the method of equipotent doses (Furchgott-Bursztyn method), and structure-activity analysis of oxytocin-like peptides acting as competitive inhibitors of oxytocin, turned out to be suitable for pharmacological analysis of this receptor system.     

Two new aminopeptidases from Ochrobactrum anthropi active on D-alanyl-p-nitroanilide

Two new enzymes which hydrolyse D-alanyl-p-nitroanilide have been detected in Ochrobactrum anthropi LMG7991 extracts. The first enzyme, DmpB, was purified to homogeneity and found to be homologous to the Dap protein produced by O. anthropi SCRC C1-38 (ATCC49237). The second enzyme, DmpA, exhibits a similar substrate profile when tested on p-nitroanilide derivatives of glycine and L/D-alanine, but the amounts produced by the Ochrobactrum strain were not sufficient to allow complete purification. Interestingly, the DmpA preparation also exhibited an L-aminopeptidase activity on the tripeptide L-Ala-Gly-Gly but it was not possible to be certain that the same protein was responsible for both p-nitroanilide and peptide hydrolysing activities. The gene encoding the DmpA protein was cloned and sequenced. The deduced protein sequence exhibits varying degrees of similarity with those corresponding to several open reading frames found in the genomes of other prokaryotic organisms, including Mycobacteria. None of these gene products has been isolated or characterised, but a tentative relationship can be proposed with the NylC amidase from Flavobacterium sp. K172. Received 7 December 1998; received after revision 15 March 1999; accepted 22 March 1999     

Analysis of structural features responsible for the sweetness of the sesquiterpene,hernandulcin

Summary The relationship between sweetness and structure was studied for several analogues of the intensely sweet sesquiterpene, hernandulcin. These derivatives were prepared synthetically, and were subjected to spectroscopic and conformational analysis. With the exception of the parent substance, none of the derivatives tested proved to be sweet. Evidence gathered in this study suggests that hernandulcin binds to its putative receptor through a three-point interaction, involving the C-1 carbonyl and C-1 hydroxyl groups, and the double bond between C-4 and C-5. In the course of a preliminary safety assessment, the 3-desmethyl derivative of hernandulcin was found to be mutagenic towardSalmonella typhimurium strain TM677.Acknowledgments. We thank Drs A. J. Hopfinger and R. Pearlstein for helpful suggestions concerning the use of CHEMLAB software, and Mr E. F. Robbins of the Research Resources Center, University of Illinois at Chicago for helpful assistance with the MS determinations. During the course of this investigation, one of us (C.M.C.) was affiliated with the Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, and the gratefully acknowledges the support and encouragement of the late Professor Martin P. Schulman. J. M. P. is the recipient of a Research Career Development Award from the National Cancer Institute (1984–1989).Paper 14 in the series Potential Sweetening Agents of Plant Origin. For paper 13, see Nanayakkara, N. P. D., Hussain, R. A., Pezzuto, J. M., Soejarto, D. D. and Kinghorn, A. D., J. med. Chem., in press.     

Enantiomeric cannabinoids: stereospecificity of psychotropic activity

Summary The 1,1-dimethylheptyl homolog of (–)-(3R,4R)-7-hydroxy-delta-6-tetrahydrocannabinol (compoundII) is highly psychotropic in mice, rats and pigeons. The (+)-(3S,4S) enantiomer (III) was found to be psychotropically inactive at doses up to several thousand times those of the ED₅₀ of (II).We thank Dr A. Breuer and Mrs H. Amsalem for help with the syntheses. The research reported above was supported in Tucson by NIH grant NS 15441; in Uppsala by grants from the Swedish Medical Research Council (5757) and the Swedish Council for the Planning and Coordination of Research (84/2082); in Jerusalem by the Szold Foundation.Presented in part at a meeting at the US National Institute on Drug Abuse, Washington, D.C., October 1986, see NIDA Research Monographs79 (1987) 15.     

Control of pheromone quantity in odor trails of the antAcanthomyops interjectus MAYR

Zusammenfassung Die Menge Spurpheromon in den Duftspuren der AmeisenartAcanthomyops interjectus wird der Qualität des Futters angepasst. Mit zunehmender Konzentration des gebotenen Zuckerwassers erhöht sich der Prozentsatz spurenlegender Ameisen. Jedes spurenlegende Tier setzt zudem mehr Duftmarken pro Wegeinheit. Gleichzeitig nimmt auch die Menge Spursubstanzlösung zu, die pro Marke ausgeschieden wird. Da die Anzahl der von einer Duftspur angelockten Nestinsassen mit zunehmender Pheromonmenge ansteigt, wird angenommen, dass dieser dreifache Kontrollmechanismus die Zahl der ausschwärmenden Arbeiterinnen der Futterqualität entsprechend reguliert.     

Acceleration of crypt cell proliferation by acoustic stimuli

Summary Cell proliferation rates in the bases of the crypts of Lieberkuhn in the jejunum of rat were measured using a stathmokinetic technique. In rats subjected to recurring loud noise cell proliferation was more rapid than in rats not subjected to the noise.     

未来化学学科的发展趋势

回顾了20世纪化学学科的发展,明确提出化学在推动人类进步和科技发展中起了核心科学的作用,论述了未来化不科发展趋势才研究模式,探讨了相关学科中的基本化学问题。     

取代联苯类化合物单一和联合毒性的定量构效关系研究

对18个取代联苯类化合物的单一毒性进行了定量结构活性相关(QSAR)分析,建立了最优模型及正辛醇/水分配系数(lgK_(ow))模型。分析表明,量子化学参数模型能很好地预测取代联苯的单一毒性,-lgEC_(50)=0.575 lgK_(ow)-40.827 RE_(max,C-H)-3.84010~(-6)-DIP+449.109(R~2=0.930,S~2=0.074,F=76.477,p0.001)。研究了混合物的联合毒性,根据浓度相加效应预测了混合物半数效应浓度(EC_(50mix)),在排除混合化合物的反应效应后,预测值与实验值较吻合。R~2=0.943。实验结果证明,QSAR模型对于单一化合物及混合化合物的毒性预测具有重要价值。     

Opposite responses of muscle circulation to different emotional stimuli

Résumé La circulation musculaire du chat est influencée par les situations émotives: la vue d'un autre chat, agresseur, cause une vasoconstriction de nature adrénergique, tandis que la vue d'un chien cause une vasodilatation de nature cholinergique.

---

---

On leave from the Department of Psychology, University of California, Los Angeles (California, USA).     

Reaction patterns of dark- and light-adaptedHydra to light stimuli

Zusammenfassung Die Kontraktionsintensität bleibt auch dann unverändert, wenn die Polypen vonHydra attenuata dem Dunkel-Hell-Wechsel (je 2 min) während 3 h ausgesetzt werden. Dunkeladaptierte Hydren reagieren auf Lichtreize auffallend empfindlicher als bei 3000 Lux helladaptierte Tiere.

---

---

These investigations were generously supported by a grant (No. 3991) from the Schweizerische Nationalfonds zur Förderung der wissenschaftlichen Forschung.     

Chemistry of some potent animal toxins

Conclusion I have discussed in this article only the most active toxins, with the result that many interesting substances have been omitted, e.g. the toxins from bee and wasp venoms (apamin, melittin, etc.), of many amphibians (bufotoxins, etc.), ciguatoxins, and many more. Poisons are found in every phylum except birds. Shrews exemplify venomous mammals. One gets a good illustration of the number of poisonous animals by studying the monumental and impressive work byHalstead ¹⁰⁶ which consequently excludes terrestrial animals. An interesting fact in this connection is that there are about 20,000 species of spiders, most of which are poisonous.A toxin ranking list has to be included in an article of this kind. The list is, of course, far from complete. Data on molecular weights, mouse lethal doses, etc. are lacking for many potent toxins, such as the dysentery toxin, a neurotoxin with a toxicity comparable to that of the botulinus toxins¹⁰⁷, the toxins from the jelly fishChironex fleckeri ¹⁰⁶.A comparison on molar basis gives a better notion of the toxicities. Curare has about 1/30 of the toxicity of the curarimimetic snake venom neurotoxins, clearly indicating that curare has a much lower affinity for the acetylcholine receptor.Toxic organisms have developed during millions of years more and more refined toxins, and this evolution has probably brought into existence toxins against every physiological function. Neurochemistry is to a great extent unexplored. Progress in this field will in the nearest future depend on specific toxins from various natural sources. Toxins from spiders, scorpions, snakes, frogs, and fishes are therefore not mere curiosities but valuable tools for research on the molecular mechanisms of neural function and synaptic transmission.