PURPOSE: This study was designed to investigate the effects of polyamines on rabbit seminal vesicular contractility. MATERIALS AND METHODS: The polyamines; putrescine, spermidine and spermine, were added to deepithelized and precontracted seminal vesicle strips, with either 10 4M norepinephrine (NE), 10 4M acetylcholine (ACh) or 70mM KCl, in organ chambers to obtain cumulative concentration response curves. A whole cell mode patch clamp study was also performed to observe the effects of the polyamines on the L-type calcium channel activities. RESULTS: The polyamines elicited concentration-dependent relaxations of the precontracted strips with the NE, ACh and KCl. The spermine showed the most potent relaxation response. Both extracellular and intracellular application of the spermine decreased the L-type calcium channel currents. CONCLUSIONS: Spermine more potently inhibited the seminal vesicle contraction than putrescine or spermidine, which suggests the polyamines may play a role in maintaining the basal tonicity of seminal vesicle in a flaccid state. The spermine-induced relaxation response seems to be related with an inhibition of the L-type calcium channel activities.
Acetylcholine ; Calcium Channels, L-Type ; Norepinephrine ; Polyamines* ; Putrescine ; Relaxation* ; Seminal Vesicles* ; Spermidine ; Spermine

Interactions among dexamethasone, dehydroepiandrosterone (DHEA), lipopolysaccharide (LPS), and antimycin A on the glutamate uptake and the polyamine uptake were investigated in primary cultures of rat cerebral cortical astrocytes to examine the effects of dexamethasone and DHEA on the regulatory role of astrocytes in conditions of increased extracellular concentrations of glutamate or polyamines. 1. (3H)Glutamate uptake: LPS and antimycin A decreased Vmax, but both drugs had little effect on Km. Dexamethasone also decreased basal Vmax without any significant effect on Km. And dexamethasone further decreased the antimycin A-induced decrease of Vmax. DHEA did not affect the kinetics of basal glutamate uptake and the change by LPS or antimycin A. 2. (14C)Putrescine uptake: LPS increased Vmax, and antimycin A decreased Vmax. They showed little effect on Km. Dexamethasone decreased Vmax of basal uptake and further decreased the antimycin A-induced decrease of Vmax, and also decreased Vmax to less than control in LPS-treated astrocytes. DHEA did not affect Km and the change of Vmax by LPS or antimycin A. 3. (14C)Spermine uptake: Antimycin A decreased Vmax, and LPS might increase Vmax. Km was little affected by the drugs. Dexamethasone decreased basal Vmax and might further decrease the antimycin A-induced decrease of Vmax. And dexamethasone also decreased Vmax to less than control in LPS-treated astrocytes. DHEA might increase basal Vmax and Vmax of LPS-treated astrocytes. 4. Vmax of glutamate uptake by astrocytes was increased by putrescine (1000 muM & 2000 muM) and spermidine (200 muM, 500 muM & 2000 muM). Spermine, 200 muM (and 100 muM), also increased Vmax, but a higher dose of 2000 muM decreased Vmax. Km of glutamate uptake was not significantly changed by these polyamines, except that higher doses of spermine showed tendency to decrease Km of glutamate uptake. In astrocytes, dexamethasone inhibited the glutamate uptake and the polyamine uptake in normal or hypoxic conditions, and the polyamine uptake might be stimulated by LPS and DHEA. Polyamines could aid astrocytes to uptake glutamate.
Animals ; Antimycin A* ; Astrocytes* ; Dehydroepiandrosterone* ; Dexamethasone* ; Glutamic Acid* ; Kinetics ; Polyamines ; Putrescine ; Rats* ; Spermidine ; Spermine

In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage- dependent calcium current (VDCCL). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current (IBa), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner (IC50=1.1+/-0.11 mM). Relationship between inhibition of contraction and calcium current by spermidine was studied using 50 mM high K+-induced contraction: Spermidine (5 mM) significantly reduced high K+(50 mM)-induced contraction to 37+/-4.7% of the control (p<0.05), and inhibitory effect of spermidine on IBa was also observed at a wide range of test potential in current/voltage (I/V) relationship. Pre- and post-application of spermidine (5 mM) also significantly inhibited carbachol (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)-induced contraction which is activated by Ca2+-induced Ca2+release (CICR),` was also inhibited by pretreatment of spermidine (5 mM). These findings suggest that spermidine inhibits spontaneous and CCh-induced contraction via inhibition of VDCCL and Ca2+releasing mechanism in guinea-pig stomach.
Acetylcholine ; Caffeine ; Calcium ; Calcium Channels ; Carbachol ; Contracts ; Muscle, Smooth ; Putrescine ; Relaxation ; Spermidine ; Spermine ; Stomach

Polyamines are non-specific marker of cellular proliferation in many malignant tumors, and it is also increase in certain benign conditions. We measured the urinary polyamines to investigate the possibility as a marker of abnormal prostate growth and the correlation with various clinical parameters. Urinary polyamine concentrations in 27 cases of symptomatic benign prostatic hyperplasia (BPH) were compared with those in 32 cases of age matched normal controls. Urinary concentration of polyamine profiles were quantitatively determined by Gas Chromatography/Nitrogen Phosphorus Detector and they were calculated by the correction of gram creatinine. The concentrations of N-acetyl putrescine, N-acetyl cadaverine, spermidine(spd), N1-acetyl spermidine, N8-acetyl spermidine, and spermine(spm) showed significant increase in BPH compared with normal control(all p<0.05). Level of serum prostate specific antigen(PSA) in BPH patients was negatively correlated with the concentration of urinary spermidine(p=0.049). And the ratio of spm/spd correlated with the level of prostate volume(p=0.046). No significant correlations was found between other clinical parameters such as age, level of hemoglobin or erythrocyte count with polyamine profiles concentration. These data suggested that urinary concentration of polyamines in BPH are elevated compared with those in normal control. Altered regulation of the biosynthesis and metabolism of spermidine and spermine may be involved in BPH.
Cadaverine ; Cell Proliferation ; Creatinine ; Erythrocyte Count ; Humans ; Metabolism ; Phosphorus ; Polyamines ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Putrescine ; Spermidine ; Spermine

OBJECTIVES: This study was designed to examine whether melatonin has a neuroprotective effect against hippocampal neuronal damage following transient global ischemia in a gerbil. Polyamine is known to play a role in the pathophysiology of ischemic neuronal damage, we evaluated the influences of melatonin on the polyamine level as well as histology. MATERIAL AND METHODS: Male Mongolian gerbils (60-80 g) were used in this study. Transient global ischemia was induced by occlusion of the bilateral common carotid arteries for 3 min with microclips. Melatonin was administered immediately after occlusion. The animals were decapitated 24 h after the occlusion for polyamine measurement by a high performance liquid chromatography (HPLC) and 4 days after the occlusion for histological evaluation (hematoxylin and eosin staining). A histological examination was performed by a blinded investigator. RESULTS: The hippocampal putrescine level increased compared to sham-operated animals and the increase of putrescine was attenuated by 20 mg/kg melatonin administration. Spermidine and spermine levels didn't show significant changes after ischemia. Hippocampal neuronal damage in the CA1 region was markedly observed in vehicle-treated animals compared to sham-operated animals. Melatonin administration (10 or 20 mg/kg) significantly inhibited hippocampal CA1 neuronal damage after ischemia compared to corresponding vehicle-treated animals (p<0.05 and p<0.01, respectively). CONCLUSION: Melatonin attenuates the putrescine level after transient global ischemia and may have putative neuroprotective effects against global ischemia induced neuronal damage.
Animals ; Brain* ; Carotid Artery, Common ; Chromatography, Liquid ; Eosine Yellowish-(YS) ; Gerbillinae* ; Hippocampus ; Humans ; Ischemia* ; Male ; Melatonin* ; Neurons* ; Neuroprotective Agents ; Putrescine ; Research Personnel ; Spermidine ; Spermine

BACKGROUND: We designed this study to examine whether melatonin has a neuroprotective effect against hippocampal neuronal damage following transient global ischemia in a gerbil. Because polyamine is known to participate in the process of ischemic neuronal damage, we examined the influence of melatonin on the polyamine level as well as histology. In particular, we examined the difference between pre- and post-ischemic treatments of melatonin by using the above mentioned parameters. METHODS: Male Mongolian gerbils (60 - 80 g) were used in this study. Transient global ischemia was induced by occlusion of the bilateral common carotid arteries for 3 min with microclips. Melatonin was administered 1 h before or 1 h after occlusion. The animals were dissected 4 days after the occlusion for polyamine measurement by a high performance liquid chromatography (HPLC) and histological evaluation (hematoxylin and eosin staining). A histological examination was performed by a blinded investigator. RESULTS: The hippocampal putrescine (PU) level increased compared to sham-operated animals and the increase of PU was attenuated by melatonin administration (pre- or post-ischemic treatment). Spermidine (SD) and spermine (SM) levels didn't show significant changes after ischemia. Hippocampal neuronal damage in the CA1 region was markedly observed in vehicle-treated animals compared to sham- operated animals. Both pre- and post-ischemic melatonin administration significantly inhibited hippocampal CA1 neuronal damage compared to corresponding vehicle-treated animals (P < 0.01, respectively). CONCLUSIONS: Melatonin attenuates the polyamine response following transient global ischemia and may have putative neuroprotective effects against global ischemia-induced neuronal damage. There is no difference in neuroprotective effects of melatonin between pre- & post-ischemic treatments.
Animals ; Carotid Artery, Common ; Chromatography, Liquid ; Eosine Yellowish-(YS) ; Gerbillinae* ; Humans ; Ischemia* ; Male ; Melatonin* ; Neurons* ; Neuroprotective Agents ; Putrescine ; Research Personnel ; Spermidine ; Spermine

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.
Acrolein ; Animals ; Biomarkers ; Brain Infarction ; C-Reactive Protein ; Diacetyl ; DNA ; Early Detection of Cancer ; Eukaryotic Cells ; Humans* ; Hydrogen Peroxide ; Inflammation ; Interleukin-6 ; Lysine ; Metabolism ; Mice ; Oxidative Stress ; Oxidoreductases ; Phospholipids ; Plasma ; Polyamines* ; Putrescine ; Renal Insufficiency ; RNA ; Sensitivity and Specificity ; Spermidine ; Spermine ; Stroke

AIMTo investigate the effect of diethylstilbestrol (DES), one of the most potent endocrine disruptors, on the metabolism of polyamines in hamster epididymis.

METHODSMale golden hamsters of 7-week-old were kept under a light and dark cycle of 14 h and 10 h for 1 week to stimulate maximally the gonadal function. DES was injected subcutaneously at doses of 0.01 mg . kg(-1) . day(-1), 0.1 mg . kg(-1) . day(-1) and 1 mg . kg(-1) . day(-1) for one week.

RESULTSDES treatment caused a significant decrease in the weight of epididymis. The activity of epididymal ornithine decarboxylase (ODC) increased 1 day after DES treatment, kept at a high level for 4 days and then decreased to nearly normal level at day 7. The activity of spermidine/spermine N1-acetyltransferase (SSAT) also increased transiently after DES treatment. The contents of putrescine, spermidine, spermine and N(1)-acetylspermidine were increased 1 day approximately 4 days after DES treatment and restored to normal at day 7. All these changes showed a marked difference between the caput and the cauda.

CONCLUSIONThe polyamine biosynthesis in the hamster epididymis can be affected by DES, a xenoestrogen. DES may probably affect polyamine metabolism in the epididymis by regulating the rate-limiting enzymes involved in the polyamine biosynthesis.

Acetyltransferases ; metabolism ; Animals ; Cricetinae ; Diethylstilbestrol ; pharmacology ; Epididymis ; anatomy & histology ; drug effects ; metabolism ; Male ; Mesocricetus ; Organ Size ; drug effects ; Ornithine Decarboxylase ; metabolism ; Polyamines ; metabolism ; Putrescine ; metabolism ; Spermidine ; analogs & derivatives ; metabolism ; Spermine ; metabolism

Makgeolli, also known as Takju, is a non-filtered traditional Korean alcoholic beverage that contains various floating matter, including yeast cells, which contributes to its high physiological functionality. In the present study, we assessed the levels of beta-glucan and glutathione in various yeast strains isolated from traditional Korean Nuruk and selected a beta-glucan- and glutathione-rich yeast strain to add value to Makgeolli by enhancing its physiological functionality through increased levels of these compounds. Yeast beta-glucan levels ranged from 6.26% to 32.69% (dry basis) and were strongly species-dependent. Dried Saccharomyces cerevisiae isolated from Nuruk contained 25.53 microg/mg glutathione, 0.70 microg/mg oxidized glutathione, and 11.69 microg/g and 47.85 microg/g spermidine and L-ornithine monohydrochloride, respectively. To produce functional Makgeolli, a beta-glucan- and glutathione-rich yeast strain was selected in a screening analysis. Makgeolli fermented with the selected yeast strain contained higher beta-glucan and glutathione levels than commercial Makgeolli. Using the selected yeast strain to produce Makgeolli with high beta-glucan and glutathione content may enable the production of functional Makgeolli.
Alcoholic Beverages ; Glutathione Disulfide ; Glutathione* ; Mass Screening ; Saccharomyces cerevisiae ; Spermidine ; Yeasts*

The effects of DFMO or/and putrescine on the dexamethasone-induced apoptosis of CEM cells were studied to investigate the role of polyamines in anti-leukemic glucocorticoid action. Dexamethasone-induced apoptosis was preceded by significant decreases of cellular polyamine contents and putrescine uptake activity. But DFMO produced decreases of putrescine and spermidine contents and marked increase of putrescine uptake activity, but did not induce apoptosis. However, dexamethasone and DFMO, respectively, induced G|1-arrest in cell cycle and hypophosphorylation of pRb, resulting in the increase of G|1 to S ratio and decrease of CEM cell count. DFMO enhanced the dexamethasone-induced apoptosis and G|1-arrest. On the other hand, putrescine little affected the apoptotic and G|1-arresting activities of dexamethasone, but almost suppress the effects of DFMO and also the DFMO-dependent enhancement of dexamethasone effects. These results suggested that the dexamethasone-induced apoptosis to be associated with pRb hypophosphorylation and G|1-arrest in CEM cells might be ascribed to the concomitant decreases of cellular polyamine contents and putrescine uptake activity.
Apoptosis* ; Cell Count ; Cell Cycle ; Dexamethasone ; Hand ; Humans* ; Polyamines ; Putrescine ; Spermidine