Effect of experimental diabetes on ornithine decarboxylase activity of rat tissues

Measurements have been made of the activity of ornithine decarboxylase of liver, heart, kidney and brain in alloxan-diabetic and control rats. In all these tissues this enzyme had decreased markedly at four weeks after induction of diabetes. These results are discussed in relation to the hormonal control and cyclic nucleotide regulation of ornithine decarboxylase.     

Effect of beta-endorphin on G-cells in rats with experimental duodenal ulcer

Immunohistochemistry was used to study the changes in the number of G cells in the antral part of the stomach of rats (40 animals) with cystamine-induced duodenal ulcer treated with beta-endorphine. In the stomach of rats with cystamine-induced ulcer the number of G cells was discovered to be significantly increased, which was removed by an opioid peptide. Naloxone did not block the action of beta-endorphine. Thus, beta-endorphine changes the number of G cells, the drug action being not associated with opiate receptors.     

Effects of dexamethasone on the activity of histidine decarboxylase, ornithine decarboxylase, and dopa decarboxylase in rat oxyntic mucosa

Since accelerated turnover of histamine in oxyntic mucosa may be an important factor in the pathogenesis of peptic ulcers, the effect of dexamethasone and other glucocorticoids on the activity of gastric histidine decarboxylase (HDC) was studied in the rat. The activity of HDC in rat oxyntic mucosa increased significantly after dexamethasone was injected s.c. to rats at doses larger than 0.4 mg/kg body weight. The maximum response of the HDC activity to dexamethasone (4 mg/kg) was observed 8 h after the treatment. The activity of ornithine decarboxylase (ODC) increased at 4 h, while that of DOPA decarboxylase showed no significant change throughout the 16-h period following a single injection of dexamethasone. The mucosal levels of histamine, putrescine, and spermidine rose significantly after the steroid treatment, while the spermine levels remained nearly constant. There was no sex difference in these responses to dexamethasone. Betamethasone showed nearly the same effects as dexamethasone on the decarboxylase activities and the mucosal levels of diamines. Serum gastrin levels showed no significant change for the first 4 h and then rose significantly 8 and 16 h after dexamethasone treatment. Pentagastrin (0.5 mg/kg) increased the HDC activity, while it showed no significant effect on either the mucosal ODC activity or levels of polyamines and histamine. These data suggest that dexamethasone influences the metabolism of histamine and polyamines in rat oxyntic mucosa both directly and via stimulation of gastrin release.     

Lysosomal enzyme activity of the gastric mucosa in rats during experimental ulcer formation

Lysosomal membrane stability has been studied in the gastric mucosa in response to mechanical damage caused by lysosomal fractionation and release of lysosomal enzymes from mucous cells into the gastric cavity of alive animals during induction of acetic ulcer or erosive damage of the gastric mucosa resulting from intraperitoneal introduction of histamine and serotonin. It has been found that all types of ulcerogenesis in the gastric mucosa led to the decrease in lysosomal membrane stability to mechanical stress in the course of lysosomal fractionation. In addition there was a substantial release of lysosomal enzymes into the gastric cavity in different types of ulcerogenesis. The decrease in lysosomal membrane stability combined with a subsequent development of ulcers and erosions in the gastric mucosa seems indicative of the fact that lysosomal enzymes take part in the initial formation of ulcers in the gastric mucosa.     

Duodenal pepsinogens in experimental duodenal ulcer in rats

Chemically induced duodenal ulcer in rats resembles the duodenal ulcer disease in humans. The mechanism of such an ulceration is not well established. This is an attempt to show that pepsinogens may play a role in such an ulceration. Twenty-four female Sprague-Dawley rats weighing 150–175 g each were divided into four groups of six rats each. The control group (A) was given 0.5 ml of distilled water subcutaneously and experimental groups were each given cysteamine (42.5 mg/100 g body wt of rats). The rats were sacrificed at 1, 2, and 4 hr. The pepsinogen content per milligram of protein was calculated in gastric and duodenal mucosa of all groups. Cysteamine produced a marked increase in duodenal mucosal pepsinogen level; however, gastric pepsinogen levels fell and were less than half at 4 hr. This might explain why cysteamine produced only duodenal ulcers and not gastric ulcers in this experimental model.     

Effect of hexadecane on piglet epidermal ornithine decarboxylase activity

Topical application of hexadecane has been shown to induce hyperproliferation and hyperkeratosis in rodent skin. The application of hexadecane to epidermis from the backs of piglets less than 1 week old resulted in a rapid biphasic-rise in the level of ornithine decarboxylase (ODC) activity. The second phase of the elevation of activity was suppressed by cycloheximide indicating that it resulted from de novo protein synthesis. The first, cycloheximide-insensitive phase presumably represents activation of existing enzyme. The activation of this latent ODC by hexadecane was independent of extracellular calcium. A similar degree of activation was observed using the bivalent-cation ionophore A23187 which augmented the hexadecane effect implicating a rise in intracellular calcium concentration as a possible cause for the activation possibly via the receptor-mediated phospholipid hydrolysis. The time-course of the ODC activation also corresponded with a rapid fall in cAMP levels indicating a possible role for cAMP in ODC regulation.     

Ultrastructure of cardiomyocytes in the peri-infarct zone during the treatment of experimental myocardial infarct in rats using the hexapeptide dalargin

The experiments on white rats with induced myocardial infarction have studied the influence of dalargin on the infarction size and peri-infarction zone ultrastructure. 24 hours later the decrease in the infarction zone size was detected in rats who had received dalargin in a dose of 50 and 100 micrograms/kg. In the peri-infarction zone the increase in glycogen quantity, the lower degree of lipid infiltration, the increase in mitochondrial number and mitochondrial energy effectiveness coefficient were noted, as compared to control animals. Sarcolemma of cardiomyocytes from the peri-infarction zone in rats on dalargin was impermeable for colloidal lanthanum. The decrease in the infarction size under the effect of dalargin is explained by its influence on the survival of cardiomyocytes in the peri-infarction zone.     

Aortic ornithine decarboxylase activity in deoxycorticosterone/salt hypertensive rats

Previous studies from our own and other laboratories have shown that hypertension induces changes in the growth of arterial smooth muscle cells (SMC). The purpose of this study was to examine the role of ornithine decarboxylase (OrnDCase) in this process. OrnDCase, the rate limiting enzyme in polyamine biosynthesis, increases in activity early in the cell cycle, and has been used as a marker of cell growth or proliferation. Deoxycorticosterone (DOC)/salt hypertension was induced in male Wistar rats. At 1-3 day intervals of DOC/salt treatment, the aortas were removed and OrnDCase activity and DNA content were determined. The results indicated that OrnDCase activity increased as early as day 2 of DOC/salt administration, reached a peak at day 10, and fell to a baseline by day 16. DNA content increased after day 10 to levels approximately 25% greater than in controls. Significant increases in blood pressure were not observed until after day 8. The findings indicate that OrnDCase activity is stimulated by DOC/salt even before the rise in blood pressure and that factors other than blood pressure per se may be important in stimulating aortic smooth muscle cell growth in the development of hypertension.     

The dynamics of the ornithine decarboxylase activity in chronically gamma-irradiated rats]

Ornithine decarboxylase activity changes in some tissues of chronically gamma-irradiated rats (0.54 cGy/h). The radiation effect is a function of the life span of continuously exposed animals. The data obtained indicate that adaptation is possible, at a metabolic level, with the restricted chronic gamma-irradiation of animals.     

Effect of catecholamines on ornithine decarboxylase activity in the testis of immature rat

Intratesticular injection of epinephrine and norepinephrine caused stimulation of ornithine decarboxylase (ODC) activity in the testis of immature rat. The effect of epinephrine was time and dose dependant. The minimal effective dose for epinephrine was found to be 100 pg and optimal stimulation was observed with 500 ng of the drug. Maximal stimulation of ODC occurred at 2 h after the treatment and reduced significantly at 4 h reaching to control levels at 6 h. Simultaneous injection of epinephrine with dibutyryl cAMP, luteinizing hormone, follicle stimulating hormone or prostaglandin E₂ caused additional stimulation of the enzyme activity. Injection of epinephrine to norepinephrine treated animals caused additional effect. Both epinephrine and norepinephrine were found to stimulate the enzyme activity in leydig cell and seminiferous tubule fractions. These results suggest that catecholamines are also involved in the regulation of ODC activity in the testis of rat.     

Effect of prostaglandins on ornithine decarboxylase activity in the testis of immature rat

Intratesticular injection of prostaglandin E₂(PGE₂) and F_2α (PGF_2α) caused stimulation of ornithine decarboxylase (ODC) activity in the testis of immature rats. PGE₂ at a dose of 10 μg per testis was maximally effective 2 hours after the injection. Dibutyryl cyclic AMP (cAMP) and 1 methyl, 3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor, also stimulated ODC activity. Simultaneous injection of PGE₂ and FSH or LH caused additional stimulation of ODC activity. Similarly injection of PGE₂ in addition to cAMP or MIX also caused increased stimulation of ODC. Indomethacin (IM, 60 μg/testis) inhibited LH, FSH or cAMP induced ODC activity. However, IM at the same dose inhibited the synthesis of total proteins. These results suggest that PGE₂ and PGF_2α stimulate the activity of ODC. The action of prostaglandins may be independent of the action of gonadotropic hormones. cAMP appears to mediate the action of prostaglandins in the testis of rat.     

Effect of prostaglandins on ornithine decarboxylase activity in the testis of immature rat

Intratesticular injection of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) caused stimulation of ornithine decarboxylase (ODC) activity in the testis of immature rats. PGE2 at a dose of 10 microgram per testis was maximally effective 2 hours after the injection. Dibutyryl cyclic AMP (cAMP) and 1 methyl, 3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor, also stimulated ODC activity. Simultaneous injection of PGE2 and FSH or LH caused additional stimulation of ODC activity. Similarly injection of PGE2 in addition to cAMP or MIX also caused increased stimulation of ODC. Indomethacin (IM, 60 microgram/testis) inhibited LH, FSH or cAMP induced ODC activity. However, IM at the same dose inhibited the synthesis of total proteins. These results suggest that PGE2 and PGF2 alpha stimulate the activity of ODC. The action of prostaglandins may be independent of the action of gonadotropic hormones. cAMP appears to mediate the action of prostaglandins in the testis of rat.     

Effect of lithium chloride on ornithine decarboxylase activity in rat adrenal.

The effects of lithium chloride on ornithine decarboxylase (ODC) activity were compared in the adrenal and kidney of control (saline treated) and prolactin-treated rats. ODC activity was decreased in kidney of both groups of animals, the magnitude of the effect of lithium in the hormone-treated group varying with the time of administering the lithium relative to prolactin. The response in the adrenal was quite different. Following treatment with LiCl, there was a gradual increase in ODC activity from a low of 10-35 pmol CO2 x 30 min-1.mg protein-1 in control animals to values 20- to 30-fold greater at 5 h. In rats treated simultaneously with LiCl and prolactin, ODC activity was greater at 5 h than that observed in animals receiving either compound alone, indicating that their effects were additive. When LiCl was given 4 h after prolactin, i.e., 1 h before sacrifice, ODC activity decreased to a very low level at 5 h, as in other tissues. The increase in ODC activity in the adrenal following LiCl is of the same magnitude as the changes observed in tissues stimulated to undergo alterations in proliferation, differentiation, or metabolic or membrane activity by hormones and other external stimuli.     

Effect of Leishmania donovani lipophosphoglycan on ornithine decarboxylase activity in macrophages.

Lipophosphoglycan (LPG), a major surface molecule from Leishmania donovani, stimulated ornithine decarboxylase (ODC) activity in macrophages in a dose- and time-dependent manner. LPG stimulated the rapid increase in ODC activity within 30 min after exposure, suggesting that the interaction of LPG with its receptor stimulated a specific signal transduction pathway. However, LPG-induced ODC activity was a transient event because 3 hr after exposure to LPG, no stimulation of ODC activity was detectable. ODC activity appeared to be coupled to the activation of protein kinase C (PKC) in macrophages, as activators of PKC caused a rapid increase in the ODC activity. Macrophages pretreated with LPG for 1 hr became unresponsive to subsequent stimulation by the PKC activators 1-oleoyl-2-acetyl-glycerol and the calcium ionophore A23187. In contrast, the ability of macrophages to express ODC activity in response to the cyclic AMP analogue dibutyryl cyclic AMP was not impaired by LPG.     

Peroxynitrite inhibits the activity of ornithine decarboxylase

Polyamines are required during cell proliferation, whereas NO has anti-proliferative properties. Ornithine decarboxylase (ODC) is a critical enzyme for the synthesis of polyamines. We tested the hypothesis that the modification of ODC by peroxynitrite (OONO-), a short-lived free radical formed from NO and superoxide produces a fall in ODC activity, and therefore polyamine synthesis and cell proliferation. The treatment of a rat recombinant ODC (rODC) with OONO- resulted in a dose-dependent inhibition of rODC activity with an IC50 of approximately 100 microM. A Western blot employing a specific antibody to nitrotyrosine revealed a dose-dependent nitration of rODC tyrosine residues. When intact IEC-6 cells were treated with ONOO-, ODC activity decreased by 49%. These data suggest a correlation between ODC activity and nitration, and a possible mechanism by which NO synthesis may modulate polyamine synthesis.     

Effect of coherence time of the applied magnetic field on ornithine decarboxylase activity

Skepticism over the possibility of weak electromagnetic fields affecting cell function exists because endogenous thermal noise fields are larger than those reported to cause effects. Four-hour exposure to a 55- or 65-Hz field approximately doubles the specific activity of ornithine decarboxylase (ODC) in L929 cells. To test the idea that the cell discriminates against this thermal noise because it is incoherent, partial incoherence was introduced into the applied field by shifting the frequency between 55- to 65-Hz at intervals of tau coh--delta tau where tau coh is a predetermined time interval and delta tau much less than tau coh varies randomly from one frequency shift to the next. To obtain the full ODC enhancement, coherence of the impressed signal must be maintained for a minimum of about 10s. For tau coh = 5.0s a partial enhancement is elicited, and at 1.0s there is no response. Unfortunately coherence times of this duration are too short to solve the thermal noise puzzle.