Bidirectional fluxes of Cl- across isolated and stripped goldfish intestinal epithelium mounted in Ussing-type chambers increased after addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), suggesting an increase of the paracellular permeability for Cl-. Confirming this, the addition of 8-Br-cAMP to the stripped intestine reduced the diffusion potential generated by isosmotic serosal or mucosal replacement of part of the NaCl by mannitol. The addition of the protein kinase C (PKC) activator 4 beta-phorbol 12,13-dibutyrate (PDB), 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), or the Ca2+ ionophore A23187 was without effect on the Cl- permeability. The cAMP-specific reduction of the diffusion potential was used to screen the epithelium for the presence of receptors coupled to adenylyl cyclase. The results indicate the presence of a serotonin (5-HT) receptor, positively coupled to adenylyl cyclase but insensitive to 5-HT1-, 5-HT2-, 5-HT3-, and nonclassical 5-HT4-receptor antagonists. Addition of vasoactive intestinal polypeptide (VIP) also reduced the diffusion potential in a dose-dependent way. Epinephrine restored the diffusion potential after its reduction by 5-HT or VIP. This effect could be mimicked by the partial alpha 2-adrenergic receptor agonist clonidine and blocked by the alpha 2-antagonists yohimbine and idazoxan. The Rp diastereoisomer of cAMP, (Rp)adenosine 3',5'-cyclic phosphorothioate [(Rp)cAMPS], counteracted the effect of VIP. The results indicate that in goldfish enterocytes VIP and 5-HT reduce the ion selectivity of the tight junctions through elevation of cAMP and that activation of alpha 2-adrenergic receptors antagonize these effects.(ABSTRACT TRUNCATED AT 250 WORDS)
We studied the effects of theophylline and ouabain on isolated intestinal mucosa of the goldfish. From continuous recordings of the intracellular potential difference, we concluded that theophylline has no considerable effect on the Cl- conductance of the apical membrane. Theophylline increased transepithelial conductance and bidirectional Cl- fluxes, while Na+ fluxes did not change appreciably. Both streaming potentials and NaCl dilution potentials were immediately reduced by theophylline. Moreover, we found a striking similarity between the effects of theophylline and ouabain. Ouabain initially increased transepithelial conductance, increased bidirectional Cl- fluxes, and instantly abolished NaCl dilution potentials. Determinations of cellular cAMP levels revealed that both theophylline and ouabain increase cAMP. The phosphodiesterase inhibitor theophylline amplified the ouabain-induced rise in cAMP, suggesting that ouabain stimulates adenylate cyclase. Since elevated extracellular K+ did not affect cAMP levels, it can be ruled out that depolarization of the cell membrane due to ouabain increases cAMP. We conclude that in this epithelium both theophylline and ouabain increase the Cl- permeability of the paracellular pathway by a cAMP-dependent mechanism.
A recent analysis of the Fermi Large Area Telescope data provided evidence for a high-intensity emission of high-energy gamma rays with a E −2 spectrum from two large areas, spanning 50 • above and below the Galactic centre (the "Fermi bubbles"). A hadronic mechanism was proposed for this gamma-ray emission making the Fermi bubbles promising source candidates of high-energy neutrino emission. In this work Monte Carlo simulations regarding the detectability of high-energy neutrinos from the Fermi bubbles 4 with the future multi-km 3 neutrino telescope KM3NeT in the Mediterranean Sea are presented. Under the hypothesis that the gamma-ray emission is completely due to hadronic processes, the results indicate that neutrinos from the bubbles could be discovered in about one year of operation, for a neutrino spectrum with a cutoff at 100 TeV and a detector with about 6 km 3 of instrumented volume. The effect of a possible lower cutoff is also considered.
KM3NeT is a research infrastructure being installed in the deep Mediterranean Sea. It will house a neutrino telescope comprising hundreds of networked moorings—detection units or strings—equipped with optical instrumentation to detect the Cherenkov radiation generated by charged particles from neutrino-induced collisions in its vicinity. In comparison to moorings typically used for oceanography, several key features of the KM3NeT string are different: the instrumentation is contained in transparent and thus unprotected glass spheres; two thin Dyneema\textsuperscript{\textregistered} ropes are used as strength members; and a thin delicate backbone tube with fibre-optics and copper wires for data and power transmission, respectively, runs along the full length of the mooring. Also, compared to other neutrino telescopes such as ANTARES in the Mediterranean Sea and GVD in Lake Baikal, the KM3NeT strings are more slender to minimise the amount of material used for support of the optical sensors. Moreover, the rate of deploying a large number of strings in a period of a few years is unprecedented. For all these reasons, for the installation of the KM3NeT strings, a custom-made, fast deployment method was designed. Despite the length of several hundreds of metres, the slim design of the string allows it to be compacted into a small, re-usable spherical launching vehicle instead of deploying the mooring weight down from a surface vessel. After being lowered to the seafloor, the string unfurls to its full length with the buoyant launching vehicle rolling along the two ropes. The design of the vehicle, the loading with a string, and its underwater self-unrolling are detailed in this paper.
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