The effect of microsomal enzyme inducing drugs on reproductive function in the ewe.

A number of drugs cause marked increases in the steroid hydroxylase activity of hepatic microsomes. Beginning 2 days after estrus, 117 mature ewes were each given 14 injections over a 27-day period of phenobarbital sodium, diphenylhydantoin, chlorcyclizine HCl or phenylbutazone. Blood samples for luteinizing hormone (LH) and progesterone determination by radioimmunoassay (RIA) were taken on day 10 of the first estrous cycle (day 18 if no heat was observed) and on days 5 and 10 of the second cycle. On day 10 of the second cycle, the ewes were given an intravenous injection of 1 ml of 6% solution of pentobarbitol sodium anesthetic per 4.5 kg body weight, and the length of anesthetic sleep time was measured. The ewes were then killed and corpora lutea and liver were weighed.In 33 ewes treated with either phenobarbitol sodium or phenylbutazone, sleep time was shortened (18 min $\text{vs}$ 29 min in untreated controls, P<.01), indicating that enzyme induction had occurred. For 41 ewes treated with either chlorcyclizine HCl or diphenylhydantoin, sleep time was lengthened to 93 min (P<.01 $\text{vs}$ controls), indicating impaired liver function. Electron micrographs of liver cells verified that enzyme induction or hepatic degeneration had occurred.     

Muscarinic acetylcholine receptor activation causes inhibition of cyclic AMP accumulation, prolactin and growth hormone secretion in GH3 rat anterior pituitary tumour cells

Acetylcholine, oxotremorine and carbachol, compounds that exhibit muscarinic agonist activity, maximally inhibited basal prolactin secretion from GH3 cells by approx. 50% and intracellular cyclic AMP levels by approx. 20%. Both parameters were inhibited with similar potencies by each agonist. These inhibitory effects were blocked by a muscarinic but not by a nicotinic receptor antagonist. In the presence of VIP or IBMX, which raise intracellular cyclic AMP levels and stimulate hormone release, the degree of muscarinic inhibition was increased, but the potency remained unchanged. Similar changes in the secretory rate of prolactin and growth hormone occurred in these and in cell perifusion experiments. These results suggest that the inhibition of hormone secretion from GH3 cells by muscarinic agonists is mediated by a decrease in intracellular cyclic AMP levels.     

Olfactory rhythm in the electrical activity of the human amygdaloid nucleus

Summated electrical activity of the human amygdaloid nucleus was investigated in the neurosurgical clinic by chronically implanted electrodes. It was found that odoriferous stimulation of this structure produced bursts of rapid rhythm (20–30 cps, 30–50 µV). The quasisinusoidal waves of olfactory rhythm consist of sinusoidal components which are more pronounced within the 20–30-Hz frequency range. Spindling of 1–3 sec duration occurs at the end of inhalation and the beginning of exhalation in time with breathing. During monorhinal breathing this activity, whose amplitude depends on degree of olfactory stimulation, can only be recorded ipsilaterally. Room air also activates the amygdaloid nucleus, but less strongly than odoriferous substances: No characteristic odor-dependent differences were discovered in the frequency range of the olfactory rhythm within a 20–30-Hz band.Institute of Physiology, Kiev State University, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 1, pp. 61–69, January–February, 1986.     

Reconstitution of the Na+K+ pump of Ehrlich ascites tumor and enhancement of efficiency by quercetin

Plasma membranes from Ehrlich ascites tumor cells were solubilized by octylglucoside in the presence of phospholipids. The Na+K+-ATPase was purified from this extract by adsorption and elution from thio-Seph-arose 4B. The enzyme (specific activity, 7 mumoles of ATP hydrolyzed min-1 mg of protein -1) was reconstituted into liposomes by the octyglucoside dilution procedure. An ATP-dependent Na+ influx with low efficiency was observed. On addition of appropriate amounts of quercetin, the Na+ flux/ATP hydrolysis ratio was increased from 0.4 to 1.4.     

Inhibition of leukocyte adhesion by the in vivo and in vitro administration of cannabinoids

Cannabinoids have been shown to affect various aspects of arachidonic acid metabolism both in vivo and in vitro. Eicosanoid metabolites of arachidonate and related octadecanoate are believed to be involved in cell adhesion processes as agonists in some instances and as antagonists in other cases. This report shows data in which cannabinoids exhibit marked inhibitory effects on the adhesion of mouse peritoneal cells to polystyrene culture dishes. The effects could be seen by in vivo administration of the drugs as well as by direct exposure of the cells in vitro. The data suggest that this inhibition of adhesion is mediated by one or more products generated by stimulation of a lipoxygenase pathway.     

Determination of products of acetohydroxy acid synthase by the colorimetric method, revisited

The enzyme acetohydroxy acid synthase (AHAS, EC 4.1.3.18) catalyzes two competing reactions of physiological importance: condensation of two molecules of pyruvate to form acetolactate (AL) or condensation of pyruvate and 2-ketobutyrate to form acetohydroxybutyrate (AHB). The activity of AHAS is most frequently analyzed using the Westerfeld method, in which the acetoin formed upon decarboxylation of AL is determined by colorimetric reaction with creatine and alpha-naphthol. However, there has been confusion as to the interpretation of the results of this assay in the presence of both substrates, conditions which lead to formation of both AL and AHB. By applying this assay to enzymatically prepared samples of AL and AHB which have also been analyzed by two other independent methods, we show here that the color yield for AHB in the commonly used assay is 35-40% that for equivalent amounts of acetoin or AL. The relative color yield is not significantly affected by varying the time or temperature of various steps in the color-forming reaction. This information could in principle be used, together with an independent specific assay for AHB, to determine the composition of an AHAS product mixture; it would, however, be less accurate than a simultaneous chromatographic method.     

Assignment of a human serum glycoprotein SP-40,40 gene (CLI) to chromosome 8.

SP-40,40 is a serum glycoprotein consisting of two different subunits (alpha and beta) assembled into a dimer by disulfide bonds. Northern blot hybridization, using total RNA from several cell lines, showed that SP-40,40 is expressed in glioblastoma and testicular tumor cells, as well as hepatoma cells. Spot blot hybridization of flow-sorted human chromosomes, using a SP-40,40 cDNA fragment as a probe, localized the gene for SP-40,40 to human chromosome 8. This gene has been given the designation CLI, for complement lysis inhibitor, by the Human Gene Nomenclature Committee.