Effects of purified scorpion toxin (tityustoxin) on gastric secretion in the rat.

An i.v. bolus injection of a purified scorpion toxin (tityustoxin, TsTX) in urethane anesthetized rats induced a dramatic increase in volume, acid and pepsin output of gastric juice and a significant decrease in its pH. The maximal stimulatory effects of TsTX on gastric secretion were obtained with a dose of 0.25 mg/kg acting for 60 min. Hexamethonium did not prevent the gastric secretion evoked by TsTX, whereas atropine or cimetidine abolished partially or totally the toxin effects. Acute bilateral cervical or abdominal vagotomy did not prevent the effects of TsTX on gastric secretion, but chronic abdominal vagotomy abolished the toxin effects. Chronic antrectomy diminished the effect of TsTX on gastric secretion. In the pylorus-ligated group of rats, the gastric secretion evoked by TsTX was not different from that observed in the pylorus-intact group. It is concluded that the changes in gastric volume, acid output, pH and pepsin output induced by TsTX in the rat are due to the release of chemical mediators from postganglionic autonomic nerve fibers which would act through muscarinic and H2-receptors stimulation.

Effect of scorpion toxin on gastric histamine and acetylcholine content in the rat.

1. The effects of a purified scorpion toxin (obtained from the Tityus serrulatus venom) on gastric secretion and on histamine and acetylcholine (ACh) levels were studied in rats. 2. Intravenous injection of 0.25 mg/kg of scorpion toxin induced a marked increase in gastric secretion in anesthetized rats. 3. Scorpion toxin also increased the histamine content in both the glandular and membranous portions of gastric wall, but there was no change in ACh content. 4. Incubation of slices of gastric wall with scorpion toxin induced a release of ACh from glandular and membranous portions. No effect of the toxin was observed on tissue-bound ACh or on free and tissue-bound histamine of either portion of the gastric wall. 5. We conclude that the gastric secretion evoked by intravenous injection of scorpion toxin in the rat is due, at least in part, to release of ACh and histamine. It is suggested that the toxin also induces synthesis of both ACh and histamine in the gastric wall.

Gastric acetylcholine and histamine content of normal and Trypanosoma cruzi-infected rats.

1. The consequences of acute Trypanosoma cruzi infection for acetylcholine and histamine levels in gastric wall and for mast cells of the stomach were studied in rats. 2. Intraperitoneal infection with 4,000 trypomastigotes/g of a Y strain of Trypanosoma cruzi led to a 4-fold decrease in gastric acetylcholine level and to a 57- and 15-fold increase in histamine content in the membranous and glandular regions of the rat stomach, respectively. 3. Infection of rats with Trypanosoma cruzi also induced a 2- and 4-fold increase in mast cell numbers in the membranous and glandular regions of the muscle layer of the gastric wall, respectively, and a ganglionic inflammatory reaction with predominance of mononuclear cells. 4. We conclude that in acutely Trypanosoma cruzi-infected rats, the reduction of acetylcholine content is due to gastric denervation and that the histamine increase might be secondary to gastric denervation and/or to an increase in the number of mast cells of the gastric wall.

Effect of scorpion toxin on the enterochromaffin-like cells in normal and Trypanosoma cruzi-infected rats: a morphological study.

Intravenous injection of scorpion toxin (Tityus serrulatus) in normal and Trypanosoma cruzi infected rats did not cause ultrastructural morphologic changes on enterochromaffin-like (ECL) cells of the stomach, although it induced a significant increase of the gastric secretion. Our data seem to indicate that gastric ECL cells structure is not affected by stimulation with scorpion toxin or by acute infection with T. cruzi in the rat.

Studies of protein kinase C in the rat basophilic leukemia (RBL-2H3) cell reveal that antigen-induced signals are not mimicked by the actions of phorbol myristate acetate and Ca2+ ionophore.

Exogenous activators of protein kinase C such as PMA in combination with a Ca2+ ionophore (A23187), cause secretion in rat basophilic (RBL-2H3) cells,but they do so through stimulatory signals that are not the same as those generated by Ag or oligomers of IgE. On the one hand, the synergy between PMA and A23187 and the suppression of Ag-mediated signals (hydrolysis of inositol phospholipids and rise in concentration of cytosolic Ca2+) by PMA were totally dependent on protein kinase C. The loss of synergistic and inhibitory actions of PMA, for example, correlated with the loss of protein kinase C (as determined by immunoblotting techniques) when cells were continuously exposed to PMA. Furthermore, the permeabilization of RBL-2H3 cells resulted in the loss of both protein kinase C and the inhibitory action of PMA, but both were retained if cells were exposed to PMA before permeabilization Ag-induced secretion, on the other hand, was not as dependent on the presence of protein kinase C. The potent inhibitor of this enzyme, staurosporine, which blocked completely the secretory response to the combination of PMA and A23187, did not inhibit Ag-induced secretion except at concentrations (greater than 10 nM) that inhibited Ag-stimulated hydrolysis of inositol phospholipids as well. Also RBL-2H3 cells still showed some secretory-response (approximately 25% of normal) to Ag when cells were depleted (greater than 98%) of protein kinase C by prolonged treatment with PMA. Previous studies have indicated that the secretory response to PMA and A23187 is much lower than that elicited by Ag when the concentrations of stimulants were matched to give the same increase in concentrations of cytosolic Ca2+.

Sustained activation of phospholipase D via adenosine A3 receptors is associated with enhancement of antigen- and Ca(2+)-ionophore-induced secretion in a rat mast cell line.

The adenosine analog, N-ethylcarboxamidoadenosine (NECA), causes transient activation of phospholipase C and an enhancement of antigen-induced secretion in a rat mast cell (RBL-2H3) line via adenosine A3-receptors (Ramkumar et al., J. Biol. Chem. 268:16887, 1993) by a mechanism that is inhibited by bacterial toxins and potentiated by dexamethasone (Ali et al., J. Biol. Chem. 265:745-753, 1990). Here we show that NECA synergizes the secretory response to Ca(2+)-ionophore as well as to antigen. The ability of NECA to synergize the secretory responses persisted for 10 to 20 min, long after the early phospholipase C-mediated reactions to NECA had subsided. NECA caused, however, a dose-dependent sustained activation of phospholipase D, as indicated by the formation of [3H]phosphatidic acid, or in the presence of 0.3% ethanol, [3H]phosphatidylethanol. This activation was associated with a sustained increase in diglycerides, in protein kinase C activity and in the phosphorylation of myosin light chains by protein kinase C. The generation of diglycerides was enhanced in dexamethasone-treated cells and suppressed in cells that had been treated with cholera toxin or pertussis toxin. Collectively, the studies suggested that the generation of diglycerides via phospholipase D and the associated activation of protein kinase C were, by themselves, insufficient signals for secretion in RBL-2H3 cells, but that these reactions synergized responses to stimulants such as antigen or A23187 that caused substantial increases in [Ca2+]i.

A metabolite of halothane covalently binds to an endoplasmic reticulum protein that is highly homologous to phosphatidylinositol-specific phospholipase C-alpha but has no activity.

When the inhalation anesthetic halothane was administered to rats, a 58 kDa protein in the liver became covalently labeled by the trifluoroacetyl chloride metabolite of halothane. The amino acid sequences of the N-terminal and of several internal peptide fragments of the protein were 99% homologous to that of the deduced amino acid sequence of a cDNA reported to correspond to phosphatidylinositol-specific phospholipase C-alpha. The purified trifluoroacetylated 58 kDa protein or native 58 kDa protein, however, did not have phosphatidylinositol-specific phospholipase C activity. We conclude that the reported cDNA of phosphatidylinositol-specific phospholipase C-alpha may encode for a microsomal protein of unknown function.

Effect of scorpion toxin on the enterochromaffin-like cells in normal and trypanosoma cruzi-infected rats: a morphological study

A injeçäo intravenosa de toxina escorpiônica ( Tityus serrulatus) en ratos normais e infectados pelo Trypanosoma cruzi näo causou alteraçöes morfológicas ultra-estruturais das células enterocromafins-like (ECL) do estômago, embora tenha induzido a aumento significativo da secreçäo do suco gástrico

Gastric acetylcholine and histamine content of normal and Trypanosoma cruzi - infected rats

The consequences of acute Trypanosoma cruzi infection for acetylcholine and histamine levels in gastric wall and for mast cells of the stomach were studied in rats. Intraperitoneal infection with 4,000 trypomastigotes/g of a Y strain of Trypanosoma cruzi led to a 4-fold decrease in gastric acetylcholine level and to a 57 - and 15-fold increase in histamine content in the membranous and glandular regions of the rat stomach, respectively. Infection of rats with Trypanosoma cruzi also induced a 2- and 4-fold increase in mast cell numbers in the membranous and glandular regions of the muscle layer of the gastric wall, respectively, and a ganglionic inflammatory reaction with predominance of mononuclear cells. We conclude that in acutely Trypanosoma cruzi-infected rats, the reduction of acetylcholine content is due to gastric denervation and that the histamine increase might be secondary to gastric denervation and/or to an increase in the number of mast cells of the gastric wall