The role of dopamine in behavioral supersensitivity to muscarinic antagonists following cholinesterase inhibition

The role of brain dopamine (DA) in the enhancement of muscarinic antagonist-induced hyperactivity was investigated. The effects of atropine and scopolamine on the concentrations of DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), following DFP administration were determined. In control animals, atropine and scopolamine decreased the concentration of DA and increased the ratios of DOPAC/DA and HVA/DA in the striatum, but not in the N. accumbens - T. olfactorium (mesolimbic) area. Following a single dose of DFP, the two antimuscarinic drugs caused decreases of DA and further increases of the above ratios in both brain regions. However, following repeated DFP treatment for 2 weeks, these antimuscarinic drug-induced changes were observed only in the mesolimbic area, but not in the striatum. It is suggested that an increased DA turnover, indicated by elevated DOPAC/DA and HVA/DA ratios, underlies the muscarinic antagonist-induced hyperactivity. The well-known occurrence of muscarinic receptor down-regulation after DFP administration, could be responsible for the enhancement of the actions of muscarinic antagonists in DFP-treated animals. The observed differential effect on DA turnover in the two broad areas may involve both muscarinic and DA receptors.     

Locations and stability of Agrobacterium-mediated T-DNA insertions in the Lycopersicon genome

Summary The genomic distribution and genetic behavior of DNA sequences introduced into the tomato genome by Agrobacterium tumefaciens were investigated in the backcross progeny of 10 transformed Lycopersicon esculentum x L. pennellii hybrids. All transformants were found to represent single locus insertions based on the co-segregation of restriction fragments corresponding to the T-DNA left and right border sequences in the backcross progeny. Isozyme and restriction fragment length polymorphism (RFLP) markers were used to test linkage relationships of the insertion in each backcross family. The T-DNA inserts in 9 of the 10 transformants were mapped in relation to one or more of these markers, and each mapped to a different chromosomal location. Because only one insertion did not show linkage with the markers employed, it must be located somewhere other than the genomic regions covered by the markers assayed. We conclude that Agrobacterium-mediated insertion in the Lycopersicon genome appears to be random at the chromosomal level. No discrepancies were found between the T-DNA genotype and the nopaline phenotype in the 322 backcross progeny of the nopaline positive transformants. Backcross progeny of two nopaline negative transformants showed incomplete correspondence between the T-DNA genotype and the kanamycin resistance phenotype. No alteration of T-DNA was observed in progeny showing a discrepancy between T-DNA and kanamycin resistance. However, two kanamycin resistant progeny plants of one of these two transformants possessed altered T-DNA restriction patterns, indicating genetic instability of the T-DNA in this transformant.Journal article no. 1223 of the New Mexico Agricultural Experiment Station     

Efficacy of ivermectin against the bloodsucking insect, Rhodnius prolixus (Hemiptera, Triatominae)

Ivermectin (0.2 mg/kg body weight) caused a high mortality in nymphs and adults of Rhodnius prolixus following a single meal in mice sub-cutaneously injected with the drug. This effect was more evident in nymphs of 1st-and 2nd-instar than in older nymphs and adults. Third-instar nymphs presented a high mortality when fed on mice treated with ivermectin 24 and 48 hours previously, while mortality was significantly reduced in nymphs fed on mice treated 72 hours before. Surviving 3rd-instar nymphs did not molt. When adult females were fed once on mice treated for 24 hours with ivermectin there was a considerable reduction in egg production. This inhibition was not reversed by a second feeding on normal mice. We concluded that sub-lethal doses of ivermectin caused toxic effects interfering in the neuro-endocrine control of development and reproduction of this bloodsucking insect.     

Reaction of ethyl 2-amino-4,6-O-benzylidene-2-deoxy-d-gluconate with acetylenic esters

Ethyl 2-amino-4,6-O-benzylidene-2-deoxy-d-gluconate adds to acetylenic esters to give sugar enaminones. The following acetylene derivatives have been employed: methyl propiolate, ethyl phenylpropiolate, and dimethyl acetylenedicarboxylate (6). With compound 6, the reaction leads to a mixture of the expected enaminone and the isomeric oxazolidine derivative. The structures and configurations of the new compounds were studied by spectroscopic and chemical methods.     

A comparison of the effect of three fungicides on growth and roridin E production by Myrothecium roridum

Three fungicides, chlorothalonil, dichloran and mancozeb were studied to determine the effects on growth and production of roridin E by Myrothecium roridum in vitro. With increasing concentrations of fungicides, both growth and production of roridin E were inhibited. Of the three fungicides, chlorothalonil was much more effective in the inhibition of growth and production of roridin E, than dichloran and mancozeb.     

The molecular organization of nerve membranes

Summary The lipid content and composition from an axolemma-rich preparation isolated from squid retinal axons was analyzed.The lipids, which accounted for 45.5% of the dry weight of this membrane, were composed of 22% cholesterol, 66.7% phospholipids and 5.2% free fatty acids. The negatively charged species phosphatidyl ethanolamine (37%), phosphatidyl serine (10%) and lysophosphatidyl ethanolamine (4%) made up 51% of the phospholipids. The amphoteric phosphatidyl choline and sphingomyelin accounted for 39% and 4%, respectively.The relative distribution of fatty acids in each of the isolated phospholipids was studied. The most remarkable feature of these phospholipids was the large proportion of long-chain polyunsaturated fatty acids. The 226 acyl chain accounted for 37% in phosphatidyl ethanolamine, 21.7% in phosphatidyl choline, 17.5% on phosphatidyl serine and 20.3% in sphingomyelin (all expressed as area %).The molar fraction of unsaturated fatty acids reached 65% in phosphatidyl ethanolamine and 42.0 and 44.8% in phosphatidyl choline and phosphatidyl serine, respectively. The double bond index in these species varied between 1.0 and 2.6.The lipid composition of the axolemma-rich preparation isolated from squid retinal axons appears to be similar to other excitable plasma membranes in two important features: (a) a low cholesterol/phospholipid molar ratio of 0.61; and (b) the polyunsaturated nature of the fatty acid of their phospholipids.This particular chemical composition may contribute a great deal to the molecular unstability of excitable membranes.The preceding papers of this series were published inArchives of Biochemistry and Biophysics.     

Morphological comparison ofSqualus blainvillei andS. megalops in the Eastern Atlantic,with notes on the genus

Morphological comparisons are made from the study of 64 specimens belonging to the following species:Squalus acanihias, S. blainvillei, S. megalops andS. acutirostris. The results suggest conspecificity betweenS. acutipinnis andS. megalops. The differences betweenS. blainvillei andS. megalops in the E-Atlantic are stressed. The Indo-Pacific species calledS. blainvillei by Chen et al. (1979) is regarded in this paper as probably an undescribed species. Some consideration on the status of several nominal species and the species grouping withinSqualus are also made.     

Histamine Stimulation of Cyclic AMP Accumulation in Astrocyte-Enriched and Neuronal Primary Cultures from Rat Brain

Histamine stimulates cyclic AMP accumulation in astrocyte-enriched and neuronal primary cultures from rat brain in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine. The response in the astrocyte cultures (Emax = 304 +/- 44% over basal, EC50 = 43 +/- 5 microM) was much higher than in neuronal cultures (Emax = 24 +/- 2%, EC50 = 14 +/- 7 microM). The histamine effect in astrocytes was competitively inhibited by the H2 antagonists cimetidine (Ki = 1.1 +/- 0.2 microM) and ranitidine (Ki = 46 +/- 10 nM) but was insensitive to the H1 antagonist mepyramine (1 microM). The two selective H2 agonists impromidine and dimaprit behaved as partial agonists and showed relative potencies (139 and 0.5, respectively) consistent with an interaction with H2 receptors. The more selective H1 agonist 2-thiazolylethylamine (0.01-1 mM) did not potentiate the response to impromidine (10 microM). Thus, in contrast to what is generally observed in intact cell preparations from brain, the histamine-induced cyclic AMP accumulation in astroglial cells is mediated solely by H2 receptors. The small effect shown in neuronal cultures also appears to be mediated by H2 receptors.