Distribution of zinc in the substantia nigra of rats treated with 6-hydroxydopamine

To study the relationship between tissue accumulation of Zinc (Zn) and neurodegeneration in the nigrostriatal dopaminergic pathway,⁶⁵Zn distribution in this pathway was examined after unilateral injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra of rats. When⁶⁵ZnCl₂ was intravenously injected 4 days after treatment with 6-OHDA,⁶⁵Zn was concentrated in the ipsilateral substantia nigra 6 days after⁶⁵Zn injection. On the other hand, 19 d after treatment with 6-OHDA,⁶⁵Zn distribution in the ipsilateral substantia nigra was decreased to the level of the contralateral one. When NH₄ ⁹⁹TcO₄, which cannot go through the blood-brain barrier, was injected into rats 4 d after treatment with 6-OHDA,⁹⁹Tc was concentrated in the ipsilateral substantia nigra 30 min after⁹⁹Tc injection, but no longer detectable 6 d after injection. These results suggest that Zn is necessary for a repair process called replacement gliosis after the death of neurons and that excess Zn does not accumulate in the lesion after completion of the gliosis.     

In vivo evidence for catecholaminergic inhibition of prolactin secretion in the teleostPoecilia latipinna

Summary Injections of L-dopa in freshwater (FW) fish reduced the size of the prolactin (PRL) cell nuclei, suggesting inhibition of PRL synthesis. A single injection of 6-hydroxydopamine (6-OHDA) in one-third seawater (1/3SW) fish reduced pituitary PRL content and increased PRL cell nuclear size at 6 h and 12 h, indicating stimulation of both synthesis and release of PRL. Two daily injections of 6-OHDA in 1/3SW fish led to PRL cell nuclear enlargement and elevated pituitary PRL content at 48 h after the second injection, indicating strong stimulation of PRL synthesis. Consideration of other parameters (plasma and body sodium levels, plasma osmotic pressure) suggests that the PRL cell responses to 6-OHDA were not mediated by internal osmotic changes. Pretreatment with 6-OHDA also appeared to accelerate the PRL cell activation induced by the transfer of fish from 1/3SW to FW.L-dopa opposed the enhancement of PRL release induced by a single injection of 6-OHDA. Injections of 3,4-dimethoxyphenylethylamine (DMPEA), a specific dopamine antagonist, caused short-term depletion of pituitary PRL, indicating enhanced PRL release.These results suggest that PRL secretion is subject to catecholaminergic inhibition, probably by dopamine. Considering these findings together with previous in vitro results (Wigham et al., 1975), it appears that the PRL cells are innervated by inhibitory catecholaminergic nerve fibres.Abbreviations DMPEA 3,4-dimethoxyphenylethylamine - L-dopa L-dihydroxyphenylalanine - FW freshwater - 6-OHDA 6-hydroxydopamine - PRL prolactin - 1/3SW one-third seawater     

Effect of ovine TSH, thiourea, ovine prolactin and bovine growth hormone on plasma thyroxine and tri-iodothyronine levels in rainbow trout,Salmo gairdneri

Summary A single injection of ovine TSH (1.1 g or 2.2 g/g body weight) effected a significant (P<0.01) increase in plasma T₄ levels in rainbow trout within 9 h and 1 h respectively. In fish given the higher dose the T₄ levels were still significantly higher (P<0.01) than in the controls 24 h after the injection. Ovine TSH had no significant effect on plasma T₃ levels. Plasma T₃/T₄ ratios in fish given the higher TSH dose were significantly lower than the controls at 3 h (P<0.01), 6 h (P=0.01), 9 h and 24 h (P<0.05) while in fish given the lower dose they were significantly lower than in controls at 3 h (P<0.01), 6 h (P=0.01) and 9 h (P<0.05).T₄ levels in TSH-injected fish were significantly higher (P<0.05) than in controls after 3 and 11 injections but were not significantly different after 16 injections. Plasma T₃ and T₃/T₄ ratios did not differ significantly in fish given multiple injections of either TSH or saline.Plasma T₄ levels in fish treated with thiourea were significantly lower (Pº0.01) than in comparable controls after 6, 9 and 15 days and plasma T₃ levels were lower (P<0.05) after 15 days treatment. T₃/T₄ ratios did not differ significantly at any time period.A single injection of bovine STH (10 g/g body weight) effect a significant rise in plasma T₄ levels 9 h (P=0.05) and 24 h (P<0.01) after the injection while ovine prolactin in a similar dose was without effect. Plasma T₃ levels in saline injected fish showed a steady decline over the 24 h following the injection whereas levels in prolactin and STH injected animals tended to rise. T₃ levels in the saline-injected fish were significantly higher (P<0.01) than in prolactin and STH injected animals 1 h after the injection but were significantly lower (P<0.01) than in the hormone-treated fish 24 h after the injection. There were no significant differences in T₃/T₄ ratios in any of the groups. Multiple injections of STH effected a significant increase (P<0.05) in plasma T₄ compared with the controls; prolactin had no significant effect. There was no significant differences in plasma T₃ concentration or T₃/T₄ ratios in any of the groups.     

Pituitary cyclic AMP and plasma hormone responses to epinephrine administration in vivo

The present study was conducted to characterize the in vivo effects of epinephrine administration on levels of pituitary cyclic AMP and plasma hormones. Rats were injected with saline or epinephrine bitartrate (1 mg/kg lP) and sacrificed by decapitation 1, 5, 15, 30 or 60 min post-injection. Levels of pituitary cyclic AMP and plasma ACTH, beta-endorphin, beta-LPH, corticosterone and prolactin were determined by radioimmunoassays. The injection procedure itself was somewhat stressful as demonstrated by increased levels of plasma prolactin and ACTH 5 min following either saline or epinephrine injection. This "stress" response was rapid and short-lasting for the pituitary hormones. The response of the adrenal hormone, corticosterone, to saline injection was slower in onset and longer in duration. Pituitary cyclic AMP levels did not increase following saline injection. Epinephrine-injected animals displayed markedly elevated plasma levels of ACTH, beta-endorphin and beta-LPH at 15, 30 and 60 min as compared to control or saline-injected rats. In addition, levels of pituitary cyclic AMP were increased over 10 fold at these times. Levels of plasma prolactin, a stress-responsive hormone, were not significantly increased in epinephrine-injected animals as compared to saline-injected rats indicating that these later responses seem to be specific to epinephrine rather than to stress.     

Role of nitric oxide in a progressive neurodegeneration model of Parkinson's disease in the rat

Abstract

This study was undertaken to investigate the nitric oxide synthase (NOS) activity in the striatum following 6-hydroxydopamine (6-OHDA) induced neurodegeneration in rats. Constitutive NOS (cNOS) activity remained unaltered at 3, 7 and 14 days after lesion, while a 43% and 45% decrease was observed at 30 and 50 days, respectively. Inducible NOS (iNOS) activity was detected only on the 3rd day after lesion and not in subsequent days or the control striatum. N^G-nitro-L-arginine methyl ester (L-NAME) pretreatment blocked the amphetamine-induced rotations and inhibited the iNOS activity at the 3rd day after the 6-OHDA injection. L-NAME pretreatment also significantly restored the striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in 6-OHDA treated rats. Thus a possible role of nitric oxide in 6-OHDA induced neurodegeneration is suggested.     

Caffeine stimulates beta-endorphin release in blood but not in cerebrospinal fluid

Plasma beta-endorphin and prolactin profiles were obtained from groups of unstressed, adult male rats. The infusion of caffeine (20 mg/kg) via a chronic, indwelling intra-atrial cannula results in a prompt and sustained (2-2.5 h) rise In plasma beta-endorphin levels. The infusion of the opiate antagonist naloxone causes a modest (40%) decrease in plasma beta-endorphin and blunts the elevation in plasma beta-endorphin following caffeine administration. In contrast, plasma prolactin levels were unchanged following caffeine administration and were decreased by treatment with naloxone. Caffeine treatment did not effect CSF beta-endorphin levels or the release of beta-endorphin from hemipituitaries incubated in vitro.     

Effect of an LHRH Analog on Growth and Hormone Receptor Levels in DMBA-Induced Mammary Tumors in the Rat

Abstract

Dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in the rat are well known to be hormono-dependent. Daily injections of an LHRH agonist, [D-Ala⁶, des-Gly-NH₂¹⁰]LHRH ethylamide (LHRH-A), 1 ug daily, for 38 days results in a 35% decrease in the number of tumors present at the beginning of the experiment compared to a decline of 45% after ovariectomy and of 8% in the control group. This is accompanied by a marked reduction in ovarian LH and FSH receptors. LHRH-A treatment also resulted in reduction in the number of progesterone and prolactin receptors in the tumors. In addition, an increase in plasma LH and FSH and a decline in plasma prolactin (PRL) concentrations are observed. The mechanisms by which the LHRH agonist induces its antitumoral effect probably relate to an ovarian desensitization to LH and FSH with a concomitant decrease in circulating levels of estrogen and prolactin, two well known stimuli for the growth of DMBA-induced mammary tumors.     

Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells

6-Hydroxydopamine (6-OHDA) is a neurotoxin to produce an animal model of Parkinson's disease. 6-OHDA increased the formation of 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG), a biomarker of oxidatively damaged DNA, and induced apoptosis in human neuroblastoma SH-SY5Y cells. Iron or copper chelators inhibited 6-OHDA-induced 8-oxodG formation and apoptosis. Thus, iron and copper are involved in the intracellular oxidatively generated damage to DNA, a stimulus for initiating apoptosis. This study examined DNA damage caused by 6-OHDA plus metal ions using ³²P-5′-end-labelled DNA fragments. 6-OHDA increased levels of oxidatively damaged DNA in the presence of Fe(III)EDTA or Cu(II). Cu(II)-mediated DNA damage was stronger than Fe(III)-mediated DNA damage. The spectrophotometric detection of p-quinone and the scopoletin method showed that Cu(II) more effectively accelerated the 6-OHDA auto-oxidation and H₂O₂ generation than Fe(III)EDTA. This study suggests that copper, as well as iron, may play an important role in 6-OHDA-induced neuronal cell death.     

Prostaglandin F2α (PGF2α) and prolactin secretion in rats

Plasma prolactin and F-prostaglandins (PGF) were measured in anesthetized male Sprague-Dawley rats before and at 15, 30, 45 and 60 minutes following i.v. injection of either PGF_2α (4 mg/kg), chlorpromazine, 1 mg/kg or chlorpromazine (1 mg/kg) after pretreatment with i.p. indomethacin (2 mg/kg). Following PGF_2α administration, plasma prolactin levels increased significantly only at 15 and 30 minutes in spite of extremely high PGF levels throughout 60 minutes. Besides the expected rise in plasma prolactin, chlorpromazine caused a transient but statistically significant increase in PGF. Indomethacin blocked the chlorpromazine-induced PGF rise but not prolactin increase. Animals stressed with ether anesthesia showed elevation of plasma prolactin, which was not blocked by indomethacin although PGF concentration fell. These results indicate that PGF_2α can stimulate prolactin release. This effect does not appear to be physiologic since very high PGF levels are required. Furthermore, blockade of prostaglandin synthesis by indomethacin does not prevent the release of prolactin in response to chlorpromazine or stress. Our findings do not support a possible role of PGFs as intermediaries in prolactin release. However, it is possible that PGFs may work through other mechanisms not investigated in our study.     

Effects of enkephalin in analogues on prolactin release in the rat.

The effects of nineteen enkephalin analogues on the circulating levels of prolactin in the male rat following intraventricular injection of the peptides were determined and compared with that of Met- and Leu-enkephalin. Eleven of the 19 analogues stimulated prolactin secretion. It was found, in general, that the structure activity relationship for enkephalin stimulation of prolactin secretion was similar to that for opiate receptor activity. Analogues which contained a [DAla²] substitution were generally effective in stimulating prolonged prolactin release. Some, but not all analogues containing [DTrp²] or [DLeu⁵] were active. Analogues containing the [DTrp¹], [DPhe⁴] or [DMet⁵] substitutions were ineffective. The prolactin releasing effect of intravenous Tyr-DAla-Gly-Phe-DLeu was reversed by naloxone. Naloxone had no effect on the haloperidol- and alpha-methylparatyrosine induced increases in plasma prolactin levels. The results of these studies are discussed in the light of the suggestion that the enkephalins may function as neuroendocrine modulators.     

Regulation of β1-Adrenergic Receptor mRNA and Ligand Binding by Antidepressant Treatments and Norepinephrine Depletion in Rat Frontal Cortex

Abstract: The number of β₁-adrenergic receptor (β₁AR) binding sites is decreased by chronic antidepressant treatments, including electroconvulsive seizure (ECS) and imipramine, whereas administration of agents that deplete norepinephrine (NE) increases the number of β₁AR binding sites in cerebral cortex. The present study was carried out to examine the influence of these treatments on levels of β₁ AR mRNA in frontal cortex to study the molecular mechanisms that underlie the regulation of β₁ ARs in brain. Levels of β₁ AR mRNA were measured by RNase protection analysis using a riboprobe derived from rat β₁AR cDNA, and the levels of βAR binding were measured using the nonselective ligand [³H]CGP-12177. Studies to verify the specificity of the RNase protection assay revealed that the distribution of β₁AR mRNA was in agreement with the reported distribution of β₁AR ligand binding: Levels of β₁AR mRNA were highest in cerebral cortex or frontal cortex, intermediate in neostriatum, hippocampus, lung, and heart, and lowest in cerebellum, kidney, and liver. Chronic ECS treatment (once daily for 10 days) significantly decreased levels of βAR ligand binding and resulted in a corresponding, time-dependent down-regulation of β₁AR mRNA levels in frontal cortex. However, imipramine administration regulated levels of β₁AR mRNA in a biphasic manner, with treatments for 7–14 days increasing and treatments for 18–21 days decreasing levels of β₁AR mRNA in frontal cortex. In contrast, levels of [³H]CGP-12177 ligand binding were decreased at all time points examined (3–21 days). The influence of NE depletion, using the neurotoxin 6-hydroxy-dopamine (6-OHDA), on levels of β₁AR mRNA was also examined. Three days after 6-OHDA treatment, levels of [³H]CGP-12177 ligand binding were not altered, but 7–14 days after neurotoxin treatment, levels of ligand binding were significantly increased. In contrast, 3–9 days after 6-OHDA treatment, levels of β₁AR mRNA were significantly decreased, and 14 days after treatment, levels of β₁AR mRNA returned to control values. The results demonstrate that β₁AR mRNA and ligand binding are regulated in parallel by ECS treatment but that levels of receptor mRNA are regulated in a complex manner by imipramine or 6-OHDA treatments, not predicted by changes in ligand binding.     

Effects of colchicine and 2-Br-alpha-ergocryptine-methane-sulfonate (CB 154) on the release of prolactin and growth hormone by functional pituitary tumor cells in culture

The effects of colchicine and 2-Br-α-ergocryptine-methane-sulfonate (CB 154) on the release of prolactin and growth hormone have been studied in a clonal strain of rat pituitary tumor cells (GH₃) in monolayer culture. These cultures produce both prolactin and growth hormone and release both proteins spontaneously into the medium without storing them in large amounts. Immunological methods were used to measure both intracellular and extracellular concentrations of the hormones. Colchicine (5 × 10^?6 M for 3 hours) caused a 2- to 3-fold increase in intracellular concentrations of prolactin and growth hormone but, under basal conditions, had little or no measurable effect on the amounts of hormone accumulated in the medium during the course of the standard three hour treatment period. This latter finding evidently is due to a lag in the onset of drug action. Colchicine had little or no effect on accumulation of extracellular prolactin during the first two hours of treatment whereas such accumulation was depressed by over 60% during the third hour of treatment. Previous studies have shown that treatment of GH₃ cells with thyrotropin releasing hormone (TRH) and hydrocortisone (HC) increases both intra and extracellular levels of prolactin and growth hormone, respectively. In cultures treated with TRH (5 × 10^?8 M), colchicine (5 × 10^?6 M for 3 hours) increased intracellular prolactin by about 70% and decreased extracellular hormone by 10%. In cultures treated with HC (3 × 1O^?6 M), colchicine increased intracellular growth hormone by more than 100% and decreased medium concentrations of the hormone by 15%. Colchicine did not significantly alter total hormone (intracellular + extracellular) accumulation, cellular uptake of ³H-amino acids, or total cell protein synthesis. The synthetic ergot alkaloid, CB 154, (3.3 × 10^?6 M for 3 hours) caused an 80% increase in intracellular, and a nearly 50% decrease in extracellular, prolactin without affecting the accumulation of growth hormone, the uptake of ³H-labeled amino acids, or overall protein synthesis in the cultures. Elevation of medium potassium concentration from a basal value of 5.3 mM to 3–5 × 10^?2 M (by addition of KCl) decreased intracellular levels of prolactin by 85% and growth hormone by 55%. These effects of high potassium were blocked by colchicine and by CB 154. We conclude that colchicine, after a lag period of two hours, acts to inhibit the release of prolactin and growth hormone from GH₃ cells. By the end of three hours of treatment, this inhibition is over 60% complete in the case of prolactin. The qualitatively different effects of colchicine and CB 154 on prolactin and growth hormone release suggest that these two secretory blocking agents probably act on GH₃ cells by different mechanisms.     

Blocking c-Jun N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-Hydroxydopamine-induced Toxicity in Vitro and in Vivo

Because oxidative stress and mitochondrial dysfunction are well known contributors to Parkinson disease (PD), we set out to investigate the role mitochondrial JNK plays in the etiology of 6-hydroxydopamine-induced (6-OHDA) oxidative stress, mitochondrial dysfunction, and neurotoxicity in SHSY5Y cells and neuroprotection and motor behavioral protection in vivo. To do this, we utilized a cell-permeable peptide of the outer mitochondrial membrane protein, Sab (SH3BP5), as an inhibitor of JNK mitochondrial translocation. In vitro studies showed that 6-OHDA induced JNK translocation to the mitochondria and that inhibition of mitochondrial JNK signaling by Tat-Sab_KIM1 protected against 6-OHDA-induced oxidative stress, mitochondrial dysfunction, and neurotoxicity. Administration of Tat-Sab_KIM1 via an intracerebral injection into the mid-forebrain bundle increased the number of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta by 2-fold (p < 0.05) in animals lesioned with 6-OHDA, compared with animals treated only with 6-OHDA into the nigrostriatal pathway. In addition, Tat-Sab_KIM1 decreased the d-amphetamine-induced unilateral rotations associated with the lesion by 30% (p < 0.05). Steady-state brain levels of Tat-Sab_KIM1 at day 7 were 750 nm, which was ∼3.4-fold higher than the IC₅₀ for this peptide versus Sab protein. Collectively, these data suggest that 6-OHDA induced JNK translocation to the mitochondria and that blocking this translocation reduced oxidative stress, mitochondrial dysfunction, and neurotoxicity both in vitro and in vivo. Moreover, the data suggest that inhibitors that block association of JNKs with the mitochondria may be useful neuroprotective agents for the treatment of Parkinson disease.     

Diphenyl Diselenide Reduces Mechanical and Thermal Nociceptive Behavioral Responses After Unilateral Intrastriatal Administration of 6-Hydroxydopamine in Rats

Parkinson’s disease (PD) patients, in addition to motor dysfunction, also present alterations in pain sensation. The present study characterized the antinociceptive effects of diphenyl diselenide ((PhSe)₂) in a model of nociception induced by unilateral, intrastriatal 6-hydroxydopamine (6-OHDA) injection in rats. Male adult Wistar rats received 20 μg/3 μl of 6-OHDA (in saline solution containing 0.02 % of ascorbic acid) or 3 μl of vehicle into the right striatum (1.0 mm anterior, 3.0 mm lateral, and 5.0 mm ventral—with respect to the bregma). Thirty days after injection, rats received (PhSe)₂ intragastrically at a dose of 10 mg/kg 1 h before behavioral tests (von Frey hairs, hot plate, tail immersion, formalin, and open field). Our results demonstrated that 6-OHDA injection to rats augmented the response frequency of von Frey hairs (VHF) stimulation, besides reducing the thermal withdrawal latency in the hot plate test. Importantly, the (PhSe)₂ treatment decreased the mechanical allodynia measured by the response frequency of VHF stimulation and diminished the thermal nociception in the hot plate test in 6-OHDA-injected rats. In conclusion, these results revealed that a single oral administration of (PhSe)₂ 1 h prior to the accomplishment of the behavioral tests was effective to attenuate the increased mechanical and thermal nociception caused by a single intrastriatal 6-OHDA injection to rats. Furthermore, other clarifying studies are warranted to improve the evidence bases for future clinical use of (PhSe)₂ as a new alternative therapy for the treatment of painful symptoms associated to PD.     

The involvement of ethanol in the free radical reaction of 6-hydroxydopamine

ESR spin trapping technique was used to detect and analyze free radical formation. When 6-hydroxydomine (6-OHDA) was incubated alone or in the presence of a free radical generating system (H₂O₂ and FeSO₄), hydroxyl free radicals were observed in a concentration-dependent manner. Glutathione was found to be the most effective scavenger of the ESR signal when compared with vitamin E or Mannitol. The addition of ethanol resulted in the formation of the pure hydroxyethyl free radicals. The amount of hydroxyethyl free radicals in the system was dependent upon the concentration of ethanol and the formation of hydroxyethyl free radicals correlated well with the extent of lipid peroxidation and the loss of enzymic activity of the membrane-bound (Na⁺, K⁺)-ATPase. We suggest that in the biological system ethanol may potentiate the neurotoxicity of 6-OHDA with the formation of hydroxyethyl free radicals, which are longer-lived and far more damaging to membranes that the hydroxyl radicals. These data lead us to further hypothesize that the neuronal degeneration caused by 6-OHDA and other compounds that generate free radicals could be potentiated in the presence of ethanol.     

Effect of the prolactin-inhibiting substances bromocripton and lergotrile on hydromineral regulation in rainbow troutSalmo gairdneri

Summary Plasma Na⁺, K⁺ and osmotic pressure were measured in rainbow trout (Salmo gairdneri) following the administration of the prolactin-inhibiting substances Lergotrile and Bromocripton. Both drugs elicited a significant fall in plasma Na⁺ concentrations although a significant response to Bromocripton was apparent only in trout acclimated to distilled water.The changes in plasma Na⁺ levels and in some cases of plasma osmotic pressure following administration of the prolactin-inhibiting substances were consistent with the hypothesis that prolactin acts to maintain plasma Na⁺ levels in this salmonid species in the same manner as in other teleosts. However, since the changes in plasma ions were small (albeit significant) is is proposed that prolactin may play a less important role in osmotic and/or ionic regulation in this species than it does in other teleostean species. Conversely, it may be that the drugs effects a less complete blockage of prolactin secretion than they appear to do in mammals.Ovine prolactin, administered with the drugs, effected a partial retention of plasma Na⁺ in Lergotrile-injected fish but did not significantly modify the effect of Bromocripton. These findings are discussed in light of the proposed action of the drugs, namely that of inhibiting the release of endogenous prolactin.Both Bromocripton and Lergotrile caused a significant fall in hematocrit values. Since plasma osmotic pressure values and plasma K⁺ concentrations were not markedly affected by the drugs (except for a significant (P<0.01) reduction in plasma osmotic pressure in the Bromocriptons-injected groups maintained in distilled water) it was thought that these changes were due to a reduction in the number of blood cells in the peripheral circulation rather than to an influx of water in response to the inhibition of prolactin.     

Cardiac Post-Junctional Alpha1- and Beta-Adrenoceptors: Effects of Chronic Chemical Sympathectomy with 6-Hydroxydopamine

Abstract

α₁- and β-adrenoceptor responsiveness and binding have been examined in cardiac tissues removed from guinea-pigs pretreated with 6-hydroxydopamine (6-OHDA) for 3 weeks. Results were compared with control tissues from sham-injected animals. Chemical sympathectomy with 6-OHDA resulted in an increase in the sensitivity of post junctional β-adrenoceptor-mediated responses to isoprenaline. No such increase was observed for the α₁-adrenoceptor-mediated responses to methoxamine. The increase in β-adrenergic responsiveness was accompanied by a significant (P<0.05) 52% increase in the number of [³H]-dihydroalprenolol binding sites with no change in binding affinity. [³H]-Prazosin binding was not affected by pretreatment with 6-OHDA. The results suggest that cardiac β-but not α₁-adrenergic responsiveness is regulated by the sympathetic innervation.     

Prostacyclin (PGI2) effets on anterior pituitary hormones in the rat in vivo

Intravenous injection of 600 μg PGE₂ or PGI₂ significantly increased serum LH and prolactin levels in estradiol treated ovariectomized rats. There was no effect on serum FSH concentration. PGE₂ and PGI₂ stimulated LH release in a non-dose dependent manner, while prolactin levels were positively correlated with the dose administered following PGI₂ treatment. 6-keto-PGF_1α at a comparable dose had no effect on pituitary hormone levels. Subcutaneous administration of 1 mg/kg or 60 mg/kg PGI₂ for seven days significantly depressed serum LH level both in male and female rats. These doses had no effect on serum FSH or prolactin levels.     

Brain Arachidonic Acid Cascade Enzymes are Upregulated in a Rat Model of Unilateral Parkinson Disease

Arachidonic acid (AA) signaling is upregulated in the caudate-putamen and frontal cortex of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, a model for asymmetrical Parkinson disease. AA signaling can be coupled to D₂-like receptor initiated AA hydrolysis from phospholipids by cytosolic phospholipase A₂ (cPLA₂) and subsequent metabolism by cyclooxygenase (COX)-2. In unilaterally 6-OHDA- and sham-lesioned rats, we measured brain expression of cPLA₂, other PLA₂ enzymes, and COX-2. Activity and protein levels of cPLA₂ were significantly higher as was COX-2-protein in caudate-putamen, frontal cortex and remaining brain on the lesioned compared to intact side of the 6-OHDA lesioned rats, and compared to sham brain. Secretory sPLA₂ and Ca²⁺-independent iPLA₂ expression did not differ between sides or groups. Thus, the tonically increased ipsilateral AA signal in the lesioned rat corresponds to upregulated cPLA₂ and COX-2 expression within the AA metabolic cascade, which may contribute to symptoms and pathology in Parkinson disease.     

Effects of changes in environmental calcium on prolactin secretion in Japanese eel,Anguilla japonica

Effects of changes in environmental Ca²⁺ on the secretion of prolactin, a possible hypercalcemic hormone, were examined both in vivo and in vitro in the Japanese ecl, Anguilla japonica. Transfer of seawater- or freshwater-adapted fish to fresh water, fresh water containing 10 mmol Ca²⁺ · 1^-1 sea water, Ca²⁺-free sea water, or deionized water was accompanied by significant changes in plasma Ca²⁺ levels after 7 days, except for the fish transferred from fresh water to fresh water and from sea water to sea water. Changes in external Ca²⁺ concentrations did not affect plasma prolactin levels, although plasma prolactin levels as well as pituitary prolactin contents were significantly greater in fish in a hypotonic environment than those in a hypertonic environment, regardless of the external Ca²⁺ concentration. Hypercalcemia, induced by removal of the corpuscles of Stannius, did not alter plasma prolactin levles. Incubation of the pituitary in the medium with different Ca²⁺ concentrations (up to 2.9 mmol·l^-1) did not affect the basal release of prolactin, except at an extremely low Ca²⁺ concentration (less than 0.1 mmol·l^-1) where prolactin release was inhibited. Addition of Ca²⁺ ionophore (A23187) to the medium led to a marked and significant increase in prolactin release, indicating that an increase in intracellular Ca²⁺ stimulates prolactin release. However, the effect was not specific to prolactin cells; a similar increase was seen in growth hormone release. These results indicate that changes in environmental Ca²⁺ concentration may not be the primary factor influencing prolactin secretion in the eel; changes in environmental osmolality or Na⁺ levels seem to be more critical for the regulation of prolactin secretion.Abbreviations CSX stanniectomy - DMSO dimethylsulphoxide - DW deionized water - FW fresh water - GH growth hormone - PRL prolactin - SW sea water