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.     

Identification and possible biological relevance of spermatozoal transglutaminase

Summary Normal human spermatozoa were demonstrated by dot immunoblot analysis and immunohistochemistry to possess transglutaminase (TGase). The immunological identification of spermatozoal TGase is consistent with reports by others of its biochemical identification and suggested role in sperm motility,and provides, in view of the immunoregulatory properties of seminal plasma TGase, presumptive identification of a means whereby spermatozoa, under normal physiological conditions, may possibly be protected from immunological attack within the female reproductive tract.     

Retention of topical liposomal formulations on the cornea

Summary The ability of liposomes composed of different kinds of phospholipid materials to adhere to the surface of the cornea was studied in the rabbit. The liposomes were labelled with tracer amounts of an I¹²⁵-labelled phosphatidylethanolamine derivative and were instilled in 10 l drops onto the cornea. The retention of radioactivity was monitored. The results show that liposomes containing positively charged phospholipids are better retained than an albumin control. Thus, it may be possible to develop a drug delivery, liposome system which would permit long-term sustained release of ophthalmic drugs onto the cornea.     

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.     

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).     

Inhibition of the growth of cariogenic bacteria in vitro by plant falvanones

Phytoalexins, defensive compounds produced by plants against microbial infections, were purified fromSophora exigua (Leguminosae) and their growth inhibitory effects on oral cariogenic bacteria were determined in vitro. Among three isolated compounds, 5,7,2,4-tetrahydroxy-8-lavandulylflavanone completely inhibited the growth of oral bacteria including primary cariogenic mutans streptococci, other oral streptococci, actinomycetes, and lactobacilli, at concentrations of 1.56 to 6.25 g/ml.     

A novel mechanism for jumping in the indian ant<Emphasis Type="Italic">Harpegnathos saltator</Emphasis> (Jerdon) (Formicidae,Ponerinae)

The Indian antHarpegnathos saltator may be unique among insects in using its jumping capacity not only as an escape mechanism but also as a normal means of locomotion, and for catching its prey in flight. High-speed cinematography used to analyse the various phases of the jump suggests thatHarpegnathos employs a novel jumping mechanism to mediate these behaviours: namely the synchronous activation of its middle and hindlegs. Electrophysiological recordings from muscles or nerves in pairs of middle and hindlegs show remarkably synchronous activity during fictive jumping, supporting the synchronous activation hypothesis.Harpegnathos is not the only ant to jump, and a cladistic analysis suggests that jumping behaviour evolved independently three times during ant evolutionary history.     

The in vivo expression of the globin genes of theβ cistron in γ-,δ-, andδβ-thalassemia heterozygotes

There is considerable evidence suggesting that the switch from to and chain production after birth is due, in part, to silencing of the genes by stage-specific factors which bind to their promoters and to the competition from the adult ( and ) genes for a common enhancer element located in the locus control region. As a consequence one can expect that the increased Hb F production in adults with hereditary persistence of fetal hemoglobin or -thalassemia is directed mainly by -globin genes in cis to the deletion(s) responsible for these conditions. Here we review data on heterozygotes with -, -, or -thalassemia, who also had an^AT mutation, in cis or in trans, which was used as a marker of gene expression. The results show that a deletion affecting adult genes favors the expression of genes in cis, while the deletion of a single gene does not affect the expression of the gene in cis but leads to a faster switch postnatally.     

Pineal ‘synaptic’ ribbon numbers and melatonin synthesis of rat are resistant to guanethidine sympathectomy

Chemical sympathectomy is widely used to study the impact of the noradrenergic system on neuronal and neuroendocrine circuits. We tested the effects of intraperitoneal injections of guanethidine, an adrenergic neuron blocking agent, on selected functional parameters of the rat pineal gland which are known to be under sympathetic influence. The reliability of the method was demonstrated by the clear enophthalmus developed by experimental animals. However, neither the numbers of synaptic ribbons nor melatonin synthesis differed between treated and control rats, both parameters exhibiting the nocturnal increase seen in intact animals. These results are in striking contrast to those obtained upon chemical sympathectomy with 6-hydroxydopamine or surgical superior cervical ganglionectomy. We conclude that guanethidine is not capable of sufficiently removing noradrenergic influence from the rat pineal gland, and that this substance is thus inferior to other experimental methods of sympathectomy.