3H]ohmefentanyl preferentially binds to mu-opioid receptors but also labels sigma-sites in rat brain sections.

Ohmefentanyl has been shown to be 6300 times more potent than morphine for analgesia. The receptor binding characteristics and distribution of [3H]ohmefentanyl in rat brain sections are presented. [3H]Ohmefentanyl bound with high affinity to opioid receptors in a saturable manner (Kd = 0.95 +/- 0.08 nM, Bmax = 337 +/- 14 fmol/mg protein). We used various currently available specific mu, delta and kappa ligands to show that [3H]ohmefentanyl has a high selectivity for the mu opioid receptor. However, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) was unable to completely inhibit [3H]ohmefentanyl specific binding, while complete inhibition was observed with fentanyl derivatives and the benzomorphan derivative, ethylketocyclazocine. This remaining 20% DAGO-inaccessible [3H]ohmefentanyl specific binding did not correspond to either mu1, delta or kappa sites. Haloperidol and 1,3-di-o-tolylguanidine were able to inhibit DAGO-inaccessible [3H]ohmefentanyl specific binding, suggesting that [3H]ohmefentanyl might also bind to haloperidol-sensitive sigma sites. The topographical distribution of [3H]ohmefentanyl found by autoradiography was generally similar to that of [3H]DAGO. However, in agreement with the biochemical results, quantitative analysis revealed additional sites in several rat brain regions, the greatest discrepancies with [3H]DAGO distribution being observed in cerebellum, central grey, hippocampal formation and locus coeruleus. Finally, our results suggest that this capacity of binding to both mu and sigma sites is shared by various fentanyl derivatives.     

Early spontaneous deficiency of calcitonin renal binding sites in rats with a high incidence of calcitonin-secreting tumors (WAG/Rij)

Old rats of the WAG/Rij strain have a high incidence (50%) of medullary thyroid carcinoma, a calcitonin (CT)-secreting tumor. We have characterized and quantified the topographical distribution of [125I]salmon calcitonin (sCT) binding sites in the kidneys of this strain, as compared to Wistar CF rats (2% incidence of spontaneous medullary thyroid carcinoma). We report here that, up to 15 days of postnatal development, the distribution of CT-binding sites in the kidney of the WAG/Rij strain was quite similar to that found in developing and adult Wistar CF rats. However, from the age of 1 month, sCT-binding sites were dramatically reduced in both the medulla and the inner part of the kidney cortex, though plasma CT levels were not significantly different in both strains. Adult WAG/Rij rats bearing a transplanted tumor for 12 weeks had a high level of plasma calcitonin and exhibited an even greater reduction of both medullary and cortical sCT-binding sites. These results suggest that the modification in the CT-binding sites in WAG/Rij rats is not a consequence of a possible down regulation due to elevated circulating hormonal level but could be inherited and possibly associated with the later development of the tumor in this strain.     

Isolation and analysis of human plasma lipoproteins accumulating postrandial in an intermediate density fraction (d 1.006--1.019 g-ml)

Plasma lipoprotein patterns have generally been determined in the fasting state. However, there is evidence from turnover and dietary studies for short-living “remnants” or “intermediate particles” accumulating postprandial. In this study we have been able to identify, isolate and partially characterize by immunochemical, chemical and ultrastructural means at least two different lipoprotein populations accumulating 6 h postprandial in the intermediate density fraction d 1.006–1.019 g/ml of healthy volunteers.     

Klinische Relevanz immunserologischer Untersuchungen bei Taubenzüchterlunge

100 sera of patients suspicious of pigeon breeder's disease were tested in Ouchterlony plates for antibodies versus antigens of pigeon serum, pigeon egg and pigeon droppings, whereas immunoelectrophoresis was done with pigeon serum. Furthermore indirect immunofluorescence was performed on pigeon bowel slides. Anti-pigeonserum-albumin-antibodies were highly specific for symptomatic pigeon breeder's disease in 16 of 24 cases. The immunofluorescence assay was more sensitive but less specific. Additionally hypergammaglobulinemia occured in 88% of patients with the disease and an increase of serum IgG of 82% respectively. Only 2 of 18 patients revealed eosinophilia. No autoantibodies could be detected in any of these cases.