Odorant signal termination by olfactory UDP glucuronosyl transferase

The onset of olfactory transduction has been extensively studied, but considerably less is known about the molecular basis of olfactory signal termination. It has been suggested that the highly active cytochrome P450 monooxygenases of olfactory neuroepithelium are termination enzymes, a notion supported by the identification and molecular cloning of olfactory-specific cytochrome P450s (refs. 13-16). But as reactions catalysed by cytochrome P450 (refs 17, 18) often do not significantly alter volatility, lipophilicity or odour properties, cytochrome P450 may not be solely responsible for olfactory signal termination. In liver and other tissues, drug hydroxylation by cytochrome P450 is frequently followed by phase II biotransformation, for example by UDP glucuronosyl transferase (UGT), resulting in a major change of solubility and chemical properties. We report here the molecular cloning and expression of an olfactory-specific UGT. The olfactory enzyme, but not the one in liver microsomes, shows preference for odorants over standard UGT substrates. Furthermore, glucuronic acid conjugation abolishes the ability of odorants to stimulate olfactory adenylyl cyclase. This, together with the known broad spectrum of drug-detoxification enzymes, supports a role for olfactory UGT in terminating diverse odorant signals.     

Suppression of natural killer cell activity in mouse spleen lymphocytes by several dopamine receptor antagonists

The effects of dopaminergic receptor inhibitors such as thiothixine (D₁/D₂), fluphenazine (D₁/D₂), trifluoperazine (D₁/D₂), pimozide (D₂), flupenthixol (D₁/D₂), (+/–)-SKF 83566 (D₁), and spiperone (D₂) on splenic natural killer (NK) cell cytotoxic activities were assessed in vitro using mouse spleen lymphocytes or enriched NK cells. Both the activities of the splenic NK cell cytotoxicity and the effector-target cell conjugation were suppressed by thiothixine, fluphenazine, and trifluoperazine at concentrations from 2.64 to 14.78 M. In addition, the augmentation of the cytolytic activity of NK cells induced by interferon- or interleukin-2 was antagonized by pretreatment with these neuroleptic compounds. However, neither the splenic NK cell cytotoxicity nor the effector-target cell conjugation were affected by treatment with other neuroleptic compounds such as pimozide, flupenthixol, (+/–)-SKF 83566, and spiperone. Thus, it appears that neuroleptic compounds such as thiothixine, fluphenazine, and trifluoperazine may act through the mechanisms other than a dopaminergic pathway to affect the NK cell-target cell interaction.     

Identification of a major cytokinin in coconut milk

A major cytokinin found in coconut milk was isolted by using the tobacco callus growth-promoting assay as a guide during purification. The structure of the factor was determined to be 14-O-{3-O-[-d-galactopyranosyl-(12)--d--galactopyranosyl-(13)--L-arabinofuranosyl]-4-O-(-L-arabinofuranosyl)--d-galactopyranosyl}-trans-zeatin riboside [G₃A₂-ZR] by various NMR techniques, including heteronuclear multiple bond connectivity by 2D multiple quantum NMR (HMBC), as well as mass spectroscopy and sugar analysis. The optimum concentration of G₃A₂-ZR for cytokinin activity in the tobacco callus assay was estimated to be 5×10^–6 M, so that G₃A₂-ZR is one order of magnitude more potent than 1,3-diphenylurea and one order less potent than zeatin riboside. At least 20% of the cytokinin activity of coconut milk could be attributed to G₃A₂-ZR.     

Kininase and anti-inflammatory activities of acid carboxypeptidase from Penicillium janthinellum.

The acid carboxypeptidase from Penicillium janthinellum catalyzed the rapid release of arginine, and the slow release of phenylalanine, proline, serine and glycine from the carboxy-terminal of bradykinin at pH 4.15 to 4.8. Anti-inflammatory activity of the acid carboxypeptidase seems to suggest that the enzyme hydrolyzed bradykinin in vivo.     

Structural changes of deoxyribonucleoprotein fibres following γ-irradiation under aerobic and hypoxic conditions

Summary The DNP fibres -irradiated under aerobic condition showed a reduction of their diameter, while no remarkable changes were observed in the DNP fibres irradiated under hypoxic condition by scanning electron microscopy.     

Antitumor activity of the Isodon diterpenoids: structural requirements for the activity.

A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids of Isodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds 9 and 3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.     

3-Hydroxy-3-Methylglutaric acid and triton-induced hyperlipidemia in rats

Summary 3-Hydroxy-3-methylglutaric acid (HMG) significantly decreased cholesterol, triglyceride and phospholipid levels in whole serum, serum -lipoproteins and liver of Triton-induced hyperlipidemic rats. Therapeutically 50 mg HMG/kg is equivalent to 200 mg nicotinic acid/kg in lowering all these lipid parameters. HMG may exert its hypolipidemic effect through inhibition of lipoprotein synthesis.Acknowledgments. We are grateful to Dr.M. Saleemuddin for encouragement, Dr.P. E. Schurr, Upjohn Co. USA for generous gift of Triton W. R 1339 and Lady Tata Memorial Trust (India) for financial assistance to one of us (SYKY).     

3-Hydroxy-3-methylglutaric acid and experimental atherosclerosis in rats

Summary In rats 3-hydroxy-3-methylglutaric acid effectively counteracts the lipemic and atherosclerotic response of massive doses of vitamin D₂. It regressed the formation of atheromatous arterial lesions. Furthermore the significant decrease in serum -lipoprotein levels on HMG treatment could be due to decrease in VLDL triglyceride and cholesterol levels.Acknowledgments. The authors are indebted to Dr.W. Drell, President, Calbiochem, San Diego, California, USA, for generous gift of HMG and Lady Tata Memorial Trust, India, for providing financial assistance to one of us (S.Y.K.Y.).