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M A Bittner

Publications and source records attributed to M A Bittner.

25 records · Page 2Linked to original sources
PubMed1989

Isolated light chain of tetanus toxin inhibits exocytosis: studies in digitonin-permeabilized cells.

Previous work indicates that the heavy chain of tetanus toxin is responsible for the binding of the toxin to the neuronal membrane and its subsequent internalization. In the present study, the light chain of tetanus toxin mimicked the holotoxin in inhibiting Ca2+-dependent secretion of [3H]norepinephrine from digitonin-permeabilized adrenal chromaffin cells. Preincubation of tetanus toxin with monoclonal antibodies to the light chain prevented the inhibition by tetanus toxin. Preincubation of tetanus toxin with nonimmune ascites fluid or with monoclonal antibodies directed against the C fragment (the C-terminal of the heavy chain) or the heavy-chain portion of the B fragment did not prevent inhibition by tetanus toxin. The data indicate that the light chain is responsible for the intracellular blockade of exocytosis.

Adrenal Medulla↗
PubMed1988

Ca2+ influx causes rapid translocation of protein kinase C to membranes. Studies of the effects of secretagogues in adrenal chromaffin cells.

In bovine adrenal chromaffin cells nicotinic stimulation or a depolarizing concentration of K+ caused a rapid, transient translocation to membranes of as much as 14% of the total cellular protein kinase C activity. The quantitative relationship between membrane-bound protein kinase C and Ca2+-dependent secretion was determined in cells rendered leaky by digitonin treatment. Intact cells were incubated with various concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA) to activate and cause translocation of protein kinase C to membrane before permeabilization in the presence of Ca2+. For the same amount of membrane-bound protein kinase C, a similar degree of enhancement of Ca2+-dependent secretion occurred in cells incubated for 1 or 30 min with TPA. Translocation of as little as 2-3% of the cellular protein kinase C to the membrane enhanced Ca2+-dependent secretion by 25-30%. Muscarinic agonists caused a 5% increase in membrane-bound protein kinase C at 2 s which rapidly reversed. Nicotinic and muscarinic receptor-mediated increases in membrane-bound protein kinase C were additive at 10 s and synergistic at 3 min. Muscarinic stimulation enhanced nicotinic receptor-dependent secretion. Prior incubation with TPA caused a similar enhancement of nicotinic-mediated secretion. The data indicate that protein kinase C which is translocated within seconds of stimulation of the cells with a nicotinic agonist or elevated K+ probably enhances the secretory response immediately or soon after exocytosis begins. In addition, the muscarinic receptor-mediated enhancement of nicotinic receptor-stimulated secretion may be due to newly activated protein kinase C.

Animals↗
PubMed1988

Effects of tetanus toxin on catecholamine release from intact and digitonin-permeabilized chromaffin cells.

Tetanus exotoxin inhibited Ca2+-dependent catecholamine secretion in a dose-dependent manner in digitonin-permeabilized chromaffin cells. The inhibition was specific for tetanus exotoxin and the B fragment of tetanus toxin; the C fragment had no effect. Inhibition required the introduction of toxin into the cell, and was not seen when intact cells were preincubated with the toxin or toxin fragments. The degree of inhibition was related to the length of preincubation with toxin, as well as the concentration of toxin used. A short preincubation with toxin was sufficient to inhibit secretion, and the continued presence of toxin in the incubation medium was not required during the incubation with Ca2+. The inhibition of secretion by tetanus toxin or the B fragment was not overcome with increasing Ca2+ concentrations. Tetanus toxin also inhibited catecholamine secretion enhanced by phorbol ester-induced activation of protein kinase C. Thus, the toxin or a proteolytic fragment of the toxin can enter digitonin-permeabilized cells to interact with a component of the Ca2+-dependent exocytotic pathway to inhibit secretion.

Adrenal Medulla↗
PubMed1986

Guanine nucleotide effects on catecholamine secretion from digitonin-permeabilized adrenal chromaffin cells.

The nonhydrolyzable GTP analogue guanosine 5'-(beta, gamma-imido)triphosphate (GMP-PNP) produced an ATP-dependent but Ca2+-independent stimulation of [3H]norepinephrine release from permeabilized chromaffin cells. This stimulation of secretion was 25-35% of the secretion induced by 10 microM Ca2+. A similar Ca2+-independent stimulation was produced by other non-hydrolyzable GTP analogues. No effect was seen with a variety of other nucleotides, including GTP. The GMP-PNP effect was specifically inhibited by low concentrations of guanine nucleotides. Addition of cAMP did not mimic the Ca2+-independent GMP-PNP effect, but did slightly enhance Ca2+-dependent secretion. Pretreatment with pertussis toxin had no effect on Ca2+-dependent secretion or on the GMP-PNP effect. There was no detectable diglyceride or inositol phosphate produced during GMP-PNP treatment, and addition of diglyceride and inositol trisphosphate did not induce secretion. Guanosine 5'-(beta-thio)diphosphate (GDP-beta-S), in addition to its ability to inhibit the GMP-PNP effect, partially inhibited Ca2+-dependent secretion. At 10 microM free Ca2+, the effects of GMP-PNP and Ca2+ were nonadditive. In fact, secretion in the presence of both GMP-PNP and 10 microM Ca2+ was slightly less than secretion due to Ca2+ alone. These data suggest that a guanine nucleotide-dependent process interacts in some way with one or more components of the normal Ca2+-dependent secretory pathway. However, it may not be an intrinsic part of the mechanism underlying Ca2+-dependent secretion.

Adenosine Triphosphate↗
PubMed1984

Biphasic time-course of capsaicin-induced substance P depletion: failure to correlate with thermal analgesia in the rat.

Capsaicin (15 or 100 mg/kg, s.c.) produced thermal analgesia in the rat hot plate test (55 degrees C). Capsaicin (100 mg/kg) also caused a reduction in spinal cord substance P levels. However, the time-course of capsaicin-induced depletion of substance P levels does not correlate with the time-course of thermal analgesia. Also, substance P depletion is biphasic, suggesting that more than one mechanism is involved in capsaicin's ability to reduce substance P levels in the spinal cord.

Animals↗
PubMed1975

Uptake, elimination, and biotransformation of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) by larvae of the aquatic midge Chironomus tentans.

Accumulation of [14C]3-trifluoromethyl-4-nitrophenol ([14C]TFM) by chironomid larvae from sublethal aqueous concentrations is rapid and dependent on hardness of exposure water. TFM is readily biotransformed to at least two more polar derivatives, including sulfated TFM and TFM-glucuronide or galacturonide. Some TFM is also reduced to the phenol amine. Chironomids can quickly eliminate all TFM derivatives as well as the parent [14C]TFM.

Animals↗