Why Amphibians Are More Sensitive than Mammals to Xenobiotics

Dramatic declines in amphibian populations have been described all over the world since the 1980s. The evidence that the sensitivity to environmental threats is greater in amphibians than in mammals has been generally linked to the observation that amphibians are characterized by a rather permeable skin. Nevertheless, a numerical comparison of data of percutaneous (through the skin) passage between amphibians and mammals is lacking. Therefore, in this investigation we have measured the percutaneous passage of two test molecules (mannitol and antipyrine) and three heavily used herbicides (atrazine, paraquat and glyphosate) in the skin of the frog Rana esculenta (amphibians) and of the pig ear (mammals), by using the same experimental protocol and a simple apparatus which minimizes the edge effect, occurring when the tissue is clamped in the usually used experimental device

Facilitated transport of urea across the gall-bladder luminal membrane

Counterflow experiments demonstrate the existence of urea counter-transport on the epithelium luminal surface. This phenomenon disappears when 10(-4) M phloretin is added to the perfusion fluid. Moreover counterflow experiments made using thiourea as elicitor, demonstrate that the phenomenon is specific for the urea

Pesticides alter ion transport across frog (Pelophylax kl. esculentus) skin

We have measured, in the edible frog (Pelophylax kl. esculentus), the effect of two fungicides (8-hydroxyquinoline and captan), and four herbicides (DCMU, glyphosate, paraquat, and propachlor) on the short-circuit current, whose value gives an estimate of the net ion transport taking place across isolated skin. Glyphosate and paraquat treatment produced a modest increase in short-circuit current, corresponding to 2.6±0.7 and 4.6±0.8 μA·cm−2, whereas the other substances had a more sustained effect, ranging from 9.1±0.6 (propachlor) to 14.8±0.9 μA·cm−2 (captan), which is mainly attributable to an increase in the Na+ absorption, and, to a lesser extent, Cl− secretion. The increase in short-circuit current after pesticide treatment, was partially abolished by AF12198, indomethacin, SC58125, SQ 22536, and W7; these results suggest that pesticides, independently from their chemical structure, induce the release of interleukin-1, which triggers the activity of cyclooxygenase-2, whose products, via a concentration in intracellular cAMP and Ca2+ concentration, increase Na+ absorption. The resulting Na+ disequilibrium must be compensated for by other epithelia, with the only consequence being the dissipation of energy. However, our results are important because they indicate that pesticides interact with the basic cellular machinery, which is responsible for the myriad of biological functions of different cell types

Permeability pathways for non-electrolytes through Bufo bufo gall-bladder

Amphotericin B treatment increases the thiourea, D-xylose and mannitol fluxes and lowers those of urea, N-methyl-urea, acetamide, formamide, and N-N'-dimethyl-thiourea. The degree of flux inhibition is related to the cellular permeability of these compounds. Most probably Amphotericin B increases the permeability of all those molecules across the luminal plasma membrane, but simultaneously elicits a cellular swelling, which reduces the diffusion across the lateral plasma membranes. This effect masks the polyene effect especially for molecules showing a mainly cellular permeation pathway such as amides and lipid soluble molecules

Effect of cycloheximide on urea facilitated transport through toad gallbladder epithelium

Transepithelial urea outfluxes across toad gallbladder were determined before and after the addition of cycloheximide. The drug inhibits the movement of urea but has no effect on thiourea and antipyrine outfluxes. The inhibition of amide transport is time dependent as also shown in counterflow experiments. These results are consistent with the hypothesis that cycloheximide inhibits the synthesis of membrane proteic sites involved in urea mediated transport

Na+ and Cl- net absorption by the isolated skin of Rana esculenta

In the last five years, several measurements of 22Na+ influx (Ji) and outflux (Jo) across symmetrical parts of the isolated skin of Rana esculenta, under permanent short circuitation, were performed in our Institute. The mean value of the 22Na+ net fluxes (Ji-Jo) exceeded the mean value of the short circuit current measurements (1.14 +/- 0.04 versus 0.98 +/- 0.02 microE.cm-2.h-1, 253 experiments). Since this discrepancy could be due to a concomitant Cl- net absorption, 36Cl- unidirectional fluxes were detected under similar experimental conditions. The Cl- net flux mean value was 0.11 +/- 0.02 microE.cm-2.h-1 (316 experiments) which accounts for 70% of the discrepancy between the Na+ net flux and short circuit current. This Cl- net absorption occurred in the absence of electrochemical gradients and was very likely maintained by a Na+/K+/2Cl- cotransport located at the outermost membrane of the epithelium. In fact bumetanide challenge (10(-5) M in the external fluid) strongly inhibited 36Cl- influx and 22Na+ influx across this tissue and cleared off the discrepancy between short circuit current and sodium net flux

Facilitated transport of urea across the toad gallbladder

The toad gallbladder epithelium is much more selective than that of the rabbit especially as to the permeability of two molecules like urea and thiourea. These observations can probably be attributed to different permeation mechanisms of the 2 molecules. Neither active transport nor solvent drag can explain these phenomena. 10(-4) M phloretin strongly inhibits urea movement, but does not alter either thiourea fluxes or isotonic net water transport: these results suggest that a specific mechanism is involved in urea movement. The urea transport shows saturation kinetic which is consistent with the presence of a facilitated mechanism

Actions of tachykinins on the ion transport across the frog skin

The tachykinin-dependent stimulation of ion transport across frog skin was studied. Tachykinin stimulation was due to interaction with an NK1-like receptor as [Sar9-Met(O2)11]-Substance P (a very selective NK1 agonist) strongly stimulated SCC, whereas [beta-Ala8]-Neurokinin A 4-10 (a very selective NK2 agonist) did not. The rank order of tachykinin potency was: PG-KI > Uperolein > Hylambatin > Kassinin > Phyllomedusin > [Sar9-Met(O2)11]-Substance P > Ranatachykinin A > Physalaemin > Ranakinin > Substance P and Eledoisin > Neurokinin A. Neurokinin B, Scyliorhinin I, Urechistachykinin I and Urechistachykinin II had no effect. We conclude that the minimal structural requirements for stimulating SCC in the frog skin were the presence of: a) the C-terminal sequence Phe-X-Gly-Leu-Met-NH2; b) at least one Pro residue in the N-terminal sequence

Lack of effect by prostaglandin F2alpha on the proliferation of the HCT-8 and HT-29 human adenocarcinoma cell lines

A variety of studies have supported the finding that regular intake of aspirin or non-steroidal anti-inflammatory drugs can affect colorectal cancer carcinogenesis by decreasing the synthesis of prostaglandins (PGs). We report that PG F2alpha, in the presence of indomethacin, did not stimulate the proliferation in HCT-8 and HT-29 human colon adenocarcinoma cells. Moreover, in both cell lines fluprostenol, a specific agonist of FP receptors, did not increase intracellular Ca2+ concentration, monitored with the fluorescent dye fura-2. These results indicate that in HCT-8 and HT-29 cells: i) proliferation is not sensitive to PG F2alpha; ii) functional FP receptors are absent. Therefore, either PG F2alpha is not necessarily involved in the proliferation of colorectal mucosa or cell lines other than HCT-8 and HT-29 should be used to assess the role played by PG F2alpha in promoting cell proliferation in colon cancer

The Factors of Difference (FoD = P_frog/P_pig) and log K_ow values of atrazine, antipyrine, mannitol, paraquat, glyphosate.

<p>Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007699#pone-0007699-g002" target="_blank">Figure 2</a> were used.</p