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.     

Maternal vitamin A restriction alters biochemical development of the brain in rats

Summary The biochemical development of the fetal brain in relation to maternal vitamin A restriction was studied in rats. The vitamin A status of pregnant rats was varied by supplying low, medium and adequate amounts (6, 40, and 100 g retinol/day/kg body weight, respectively) of vitamin A during pregnancy and suckling. The maternal vitamin A restriction caused an altered brain development in terms of tissue weight, DNA, RNA and protein levels, and biosynthesis of DNA and protein from [³H]-thymidine and [³H]-leucine, respectively. A dose-dependent effect of maternal vitamin A restriction on the metabolism of DNA, RNA and protein was noticed in the developing fetal brain of rats.     

Hypothalamic histamine modulates adaptive behavior of rats at high environmental temperature

Summary Histamine content in the rat hypothalamus was lower at 4°C and higher at 31°C compared to that at 21°C. Pretreatment with -fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, attenuated both the increased level of hypothalamic histamine and rat adaptive behavior at 31°C. Increase of histamine content in the hypothalamus appears to be an important factor contributing to rat adaptive behavior to high environmental temperature.     

Evidence from carbon isotope measurements for diverse origins of sedimentary hydrocarbons

The organic matter found in sedimentary rocks must derive from many sources; not only from ancient primary producers but also from consumers and secondary producers. In all of these organisms, isotope effects can affect the abundance and distribution of 13C in metabolites. Here, by using an improved form of a previously described technique in which the effluent of a gas chromatograph is continuously analysed isotopically, we report evidence of the diverse origins of sedimentary organic matter. The record of 13C abundances in sedimentary carbonate and total organic carbon can be interpreted in terms of variations in the global carbon cycle. Our results demonstrate, however, that isotope variations within sedimentary organic mixtures substantially exceed those observed between samples of total organic carbon. Resolution of isotope variations at the molecular level offers a new and convenient means of refining views both of localized palaeoenvironments and of control mechanisms within the global carbon cycle.