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.     

Tamoxifen ‘sex reverses’ alligator embryos at male producing temperature,but is an antiestrogen in female hatchlings

Summary Tamoxifen is an anticancer drug widely used in the treatment of estrogen-dependent breast cancer. In hatchling alligators it acts as a pure antiestrogen in that it completely blocks the effect of estradiol-induced oviductal hypertrophy and completely blocks the estradiol-induced hepatic vitellogenin secretion. Paradoxically, when injected into alligator eggs incubated at 33°C, a temperature which would normally result in 100% male hatchlings, tamoxifen sex reverses the embryos into apparently normal female hatchlings.     

Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf

Mean plasma insulin concentration was reduced and mean plasma glucose concentration increased following the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mol kg^–1 i.a.) in conscious calves given continuous infusions of exogenous glucose (30–60 mol min^–1 kg^–1 i.v.). It is concluded that the rise in plasma insulin concentration which occurs in these animals in response to glucose is mediated, at least in part, by a nitric oxide-related factor (NOx).     

Nα-quinaldyl-L-arginine·HCl,a new defensive alkaloid fromSubcoccinella-24-punctata (Coleoptera,Coccinellidae)

The isolation of N-quinaldyl-L-arginine·HCl (1) from the CoccinellidaeSubcoccinella-24-punctata is reported. The structure, first established on the basis of the analysis of the spectral properties of1, has been confirmed by synthesis. The alkaloid is of endogenous origin and markedly deterrent to ants.     

Molecular evidence for increased hematopoietic proliferation in the spleen of the b/b laboratory rat

The splenomegaly and the appearance of a significant number of CFU-E (erythroid colony-forming units) and BFU-E¹ (erythroid burst-forming units) in the Belgrade laboratory rat (b/b) spleen prompted us to analyse further the molecular evidence for increased hematopoietic proliferation in the b/b spleen. Messenger RNAs (mRNAs) specific for globins, proteins for iron transport and deposition and the band 3 protein were used in rat erythropoietic tissues as markers for proliferation and erythroid differentiation. In the b/b spleen, all mRNAs analysed display an erythroid-specific pattern of expression. This analysis also revealed an enhanced level of mRNA for ferritin in the +/b spleen, whereas erythrocyte-specific mRNA production was normal.     

High-affinity binding ofβ-alanine to cerebral synaptosomes might involve glycine-receptors

Summary High-affinity, Na⁺-independent binding of -alanine to a synaptosomal fraction of rat brain was potently inhibited by glycine and by some other -amino acids, but not by taurine or GABA. This binding mechanism, which was also sensitive to both bicuculline and strychnine, might involve synaptic receptors for both -alanine and glycine.This study was supported in part by Centro Ramón y Cajal and Fundacion Juan March.     

Control of obesity inA vy /a mice by 5α-androstan-17-one

Summary Treating VY/WfL-A ^vy /a mice with 5-androstan-17-one, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented the mice from becoming obese. The weight difference between treated and controlA ^vy /a mice was mainly due to a decreased accumulation of triacylglycerol. The compound did not suppress appetite, had no detectable toxicity and did not affect the lipogenesis rates in the liver and carcass. The weight-controlling effect of 5-androstan-17-one inA ^vy /a mice was reversible upon withdrawal of treatment.The authors wish to thank Mr W.R. Gibson and Drs C.G. Culbertson and P.N. Harris for performing the pathological examinations.     

Reciprocal changes in serum free thyroxine fraction and thyrotropin level after administration of thiocyanate to rats

Summary The administration of thiocyanate to rats caused a significant increase of serum free thyroxine fraction, which coincided with the significant decrease of TSH level. The other components (AFT₄, T₄, T₃) in serum at this time were decreased or unchanged. The finding suggests the role of free thyroxine fraction in feed-back regulation of TSH secretion.Acknowledgment. We thank Dr A. Parlow and the NIAMDD, Rat Pituitary Hormone Distribution Program, for material for rat TSH immunoassay; Dr J. Nauman (Inst. Postgrad. Med., Warsaw, Poland) for T₃ antibody, and to Ing. J. Sadlo, Mrs M. t'astná and Miss R Fajkoová for technical assistance.