Characterization of sodium transport in gustatory epithelia from the hamster and rat

The transduction of sodium salts occurs through a variety of mechanisms, including sodium influx through amiloride-sensitive sodium channels, anion-dependent sodium movement through intercellular junctions and unidentified amiloride-insensitive mechanisms. Characterizations of sodium transport in lingual epithelium mounted in Ussing chambers have focused almost exclusively on epithelia containing only fungiform taste buds. In the present study we have investigated sodium transport by measuring NaCl-induced short-circuit current from lingual epithelia containing fungiform, foliate, vallate and palatine taste buds in the hamster and the rat. All areas show measurable sodium transport, yet significant differences were noted between the epithelia from the rat and the hamster and among the different epithelia within a single species in terms of current density, transepithelial resistance and mucosal amiloride sensitivity. In general, epithelia from the anterior tongue were of a lower resistance and transported sodium more effectively than from the posterior tongue. Moreover, fungiform- and vallate-containing epithelia in the rat had a greater current density than did the corresponding tissues in the hamster. Amiloride sensitivity also differed between the rat and the hamster. In the hamster all gustatory areas showed some amiloride sensitivity, while in the rat the vallate-containing epithelia were devoid of amiloride- sensitive sodium transport. The results are consistent with the interpretation that all chemosensitive areas may participate in the detection of salts but the degree of salt transport and the mechanism of transport is variable among different lingual epithelia and different species.      

Cathepsin K and matrix metalloprotease activities in bone tissue of the OXYS rats during the development of osteoporosis

The activity of osteoclast-specific cysteine protease, cathepsin K, and matrix metalloproteases (MMPs) has been investigated in bone tissue of senescence-accelerated OXYS rats and in Wistar rats. At the age of 3 month (the period preceding manifestation of osteoporosis in OXYS rats) cathepsin K activity was higher whereas MMP activity was lower in Wistar rats. At the age of 14 months Wistar rats cathepsin K activity increased and MMP activity decreased. The age-related changes in bone cathepsin K and MMP activity of OXYS rats had opposite direction. Thus, despite of marked manifestations of osteoporosis previously found by us in OXYS rats (the decrease in mineralization density of the bone tissue and its resorption) no interstrain differences in cathepsin K and MMPs were found between Wistar and OXYS rats. Activity of a universal protease inhibitor, α₂-macroglobulin, was higher in serum of 14-month old OXYS rats than in Wistar rats of the same age. The role of cathepsin K activation in resorption of bone tissue in the development of osteoporosis in senescence-accelerated OXYS rats is discussed.     

Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin

Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1 N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance.     

Role of vacuolar apparatus overload in lysosomal changes in liver cells in acute toxic hepatitis]

Physical and chemical properties of the rat liver lysosomes with single Triton WR 1339 overloading were studied during the administration of a detergent to intact rats and those with acute toxic hepatitis. Administration of the latter to intact animals was accompanied by a reduction of the floating density of the particles, solubilization of the lysosome enzymes and by increased fragility of the particles in the hypotonic medium. Lysosomes of the hepatocytes in rats with toxic hepatitis also displayed signs of overloading of the vacuolar apparatus with the preparation administered. The most pronounced solubilization of the lysosomal enzymes beta-galactosidase, acid RNA-ase, cathepsin D--was noted in case of combined action of CCl4 and Triton WR 1339 24, 48, 72 hours and 7 days after the CCl4 poisoning. Possible consequences of overloading of the vacuolar apparatus of the rat hepatocytes are discussed.     

Prognostic significance of lysosomal cysteine proteases in the estimation of the effectiveness of the antitumor therapy

The influence of the antitumor drugs, cyclophosphamide (CPA) and nitrosomethylurea (NMU) on the activity of lysosomal cysteine proteases cathepsin B and L in tumor tissue has been investigated using CPA-sensitive (LS) and CPA-resistant mouse lymphosarcomas (RLS). (These drugs exhibit high and low antitumor efficiency towards LS and RLS mouse lymphosarcomas, respectively). Regression or reduction in the growth rate of LS and RLS lymphosarcomas caused by CPA or NMU administration was accompanied by the increase in the activity of cysteine proteases cathepsin B and L in the tumor tissue. The increase of cathepsin B and L activity in tumor tissue correlated with the therapeutic effect of these drugs. Data obtained suggest that activity of cathepsin B and L in tumor tissue has a prognostic significance for the estimation of the effectiveness of antitumor therapy.