Administration Of Β-endorphin Research Articles

Временной фактор в регуляции цитокиновой секреции у мышей бета-эндорфином

Эндогенные опиоидные пептиды играют важную роль в регуляции иммунных процессов. Цель работы - изучение влияния бета-эндорфина на уровни кортикостерона в плазме периферической крови мышей, секрецию IL-2, IL-4 и IFN-gamma мышиными спленоцитами, а также продукцию IL-1b и IL-10 перитонеальными макрофагами in vivo через 1 ч и через 6 ч после введения пептида. Методика. Исследования выполнены на беспородных мышах-самцах массой 22-25 г. Бета-эндорфин вводили однократно внутрибрюшинно в дозах 100-0,0005 мкг/кг. Через 1 или 6 ч после введения бета-эндорфина животных выводили из эксперимента, выделяли перитонеальные макрофаги и спленоциты для культивирования. Результаты. Установлено, что введение бета-эндорфина в дозах 100, 0,01, 0,0005 мкг/кг за 1 ч до выведения животных из эксперимента приводило к угнетению спонтанной продукции IL-1b макрофагами. Введение пептида за 6 ч в дозе 1 мкг/кг приводило к угнетению продукции IL-1b стимулированными макрофагами. b-эндорфин выражено снижал продукцию IL-10 во всех исследуемых дозах как при введении за 1ч, так и за 6 ч до выведения животных из эксперимента. Пептид усиливал Кон А - индуцированную продукцию IL-4 как через 1 ч, так и через 6 ч после инъекции. Продукция IL-2 спленоцитами угнеталась через 1 ч после введения пептида, и стимулировалась через 6 ч после введения. На продукцию IFN-g введение b-эндорфина влияния не оказывало. Концентрация кортикостерона в плазме крови интактных мышей под воздействием b-эндорфина не изменялась. Заключение. Бета-эндорфин, несмотря на быстрое ферментативное расщепление в организме, способен оказывать пролонгированные иммуномодулирующие эффекты, которые могут менять свою направленность с течением времени. Endogenous opioid peptides play an important role in regulation of immune processes. The work objective was to study the effect of beta-endorphin on corticosterone levels in murine peripheral blood plasma, secretion of IL-2, IL-4, and IFN-g by murine splenocytes, and production of IL-1b and IL-10 by peritoneal macrophages in vivo at 1 h and 6 h following administration of the peptide. Methods. Investigations were performed on mice weighing 22-25 g. Beta-endorphin (100-0,0005 mg/kg, i.p.) was administered once. One or six hours after the beta-endorphin administration, the animals were withdrawn from the experiment, peritoneal macrophages and splenocytes were isolated for culturing. Results. Administration of beta-endorphin at doses of 100, 0.01, and 0.0005 mg/kg 1 h before sacrificing animals led to suppression of macrophage spontaneous production of IL-1b. Administration of the peptide at a dose of 1 mg/kg within 6 hours prior to sacrificing resulted in inhibition of IL-1b production by stimulated macrophages. Βeta-endorphin at all doses reduced the IL-10 production both 1 h and 6 h before sacrificing the mice. The peptide enhanced Con A-induced production of IL-4 both 1 h and 6 h after injection. Production of IL-2 by splenocytes was inhibited 1 h after administration of the peptide and stimulated 6 h after the peptide administration. Administration of b-endorphin had no effect on the IFN-g production. b-endorphin did not change plasma corticosterone concentrations in intact mice. Conclusion. Beta-endorphin, despite its rapid enzymatic cleavage, is able to exert long-term immunomodulatory effects, which can change their direction over time.

β-Endorphin in the median preoptic nucleus modulates the pressor response induced by subcutaneous hypertonic sodium chloride

Considerable evidence has been gathered involving the endogenous opioid system in blood pressure regulation. In the present study, we investigated the effect of administering β-Endorphin into the median preoptic nucleus (MnPO) on blood pressure (BP) and heart rate (HR) and whether this administration was capable of modulating the pressor response observed after an acute increase in plasma osmolality. In urethane-anaesthetized Wistar rats, different doses of β-Endorphin (1, 10, 25 ng) were microinjected into the MnPO to elucidate a putative role for β-Endorphin in BP and HR regulation. Additionally, we evaluated the modulatory effect of the β-Endorphin injection (25 ng) into the MnPO on the pressor response to subcutaneous sodium chloride solution administration (2 M NaCl, 0.1 ml/10 gbw). The MnPO-β-Endorphin microinjection resulted in a dose-dependent hypotensive and bradycardic effect and pre-treatment with the opioid antagonist, naloxone (100 ng), injected in the same nucleus, significantly antagonized the cardiovascular response to β-Endorphin administration in the MnPO. On the other hand, a microinjection of β-Endorphin (25 ng) into the median preoptic nucleus abolished the pressor response to a subcutaneous injection of hypertonic saline. It is concluded from these results that β-Endorphin-MnPO administration produces a decrease in BP and HR in normotensive animals and also inhibits the pressor response evoked by an acute increase in plasma osmolality.

Anti-analgesia and reduced antinociception from supraspinally administered β-endorphin in stressed rats: dependence on spinal cholecystokinin via cholecystokinin B receptors

Rats exposed to the stress of repeated exposure to a noxious heat source (52.5°C, hot plate) exhibit stress-induced analgesia, but reduced antinociception (detected using the tail-flick test) to the administration of β-endorphin into the periaqueductal gray region of the brain. This is accompanied by an anti-analgesic response (reduction in the stress-induced increase of tail flick latency) to doses of β-endorphin (0.03 nmol) lower than those usually associated with antinociception. These alterations are prevented and antinociceptive potency is maintained when rats are treated with cholecystokinin (CCK) antagonists intrathecally. The potency of L-365,260 and L-364,718, selective CCK B and CCK A receptor antagonists, respectively, correlated with their apparent affinities for CCK B receptors, suggesting that the altered sensitivity to β-endorphin is mediated via CCK B receptors.

Central Opioid Control of Feeding Behavior in the White-Crowned Sparrow,Zonotrichia leucophrys gambelii

Many behavioral responses to stress do not appear to be mediated by glucocorticoids, suggesting another mechanism. We tested the effects of intracerebroventricular administration of β-endorphin, a neuropeptide implicated in the stress response, on feeding behavior in captive, wild-caught white-crowned sparrows (Zonotrichia leucophrys gambelii). The amount of time spent feeding and the number of feeding bouts were higher after infusion with β-endorphin than after saline infusion. β-endorphin decreased the latency to feed compared with saline. Naloxone, an opioid antagonist, suppressed feeding behavior and increased latency to feed. These results support our hypothesis that neuropeptides associated with stress may initiate adaptive responses to natural stressors in wild species.

Cyclo(Gly-Gln) inhibits the cardiorespiratory depression produced by β-endorphin and morphine

Glycyl- l-glutamine (Gly-Gln; β-endorphin 30–31) is an endogenous dipeptide that is synthesized through the post-translational processing of β-endorphin. Previously, we showed that Gly-Gln inhibits the hypotension and respiratory depression produced by central β-endorphin administration. In this study, we tested whether cyclo(Gly-Gln), a non-polar, cyclic Gly-Gln derivative, was similarly effective following intracerebro-ventricular (i.c.v.) or intra-arterial (i.a.) administration to pentobarbital-anesthetized rats pretreated with β-endorphin (0.5 nmol i.c.v.). Intracerebroventricular cyclo(Gly-Gln) (0.3, 0.6 or 1.0 nmol) injection produced a dose-dependent inhibition of β-endorphin-induced hypotension, but not bradycardia, with a potency similar to that of Gly-Gln. Cyclo(Gly-Gln) (5 mg/kg) was also effective following i.a. injection and significantly attenuated the fall in arterial pressure elicited by i.c.v. β-endorphin, consistent with evidence that cyclic dipeptides permeate the blood–brain barrier; i.a. Gly-Gln was ineffective. Intra-arterial cyclo(Gly-Gln) (5 mg/kg) and i.c.v. Gly-Gln (10 nmol) also attenuated the hypotension and respiratory depression induced by morphine (50 or 100 nmol i.c.v.). Cyclo(Gly-Gln) (0.5, 5.0 or 50.0 mg/kg i.a.) had no effect on arterial pressure or heart rate when given alone. These findings indicate that cyclo(Gly-Gln) is a biologically active peptide capable of reversing the cardiorespiratory depression produced by β-endorphin or morphine.

Intracerebroventricular administration of β-endorphin increases the expression of c- fos and of corticotropin-releasing factor messenger ribonucleic acid in the paraventricular nucleus of the rat

We evaluated the effects of intracerebroventricular (i.c.v.) administration of β-endorphin and naloxone, an opioid antagonist, on the induction of c- fos and corticotropin-releasing factor (CRF) mRNA to clarify the effects of β-endorphin on cellular activity and CRF gene expression in the paraventricular nucleus (PVN) of the rat using in situ hybridization. A significant induction of c- fos mRNA was noted in the PVN after i.c.v. injection of β-endorphin, compared to control. This induction was inhibited by the administration of naloxone. A significant increase in CRF mRNA levels in the PVN was observed 120 min after the i.c.v. injection of β-endorphin. This increase was partially, but significantly, inhibited by naloxone administration. In addition, i.c.v. administration of β-endorphin increased plasma ACTH concentration in freely moving rats, which was inhibited by intravenous injection of CRF antiserum. These results suggest that the i.c.v. injection of β-endorphin increases the neuronal activity and the biosynthesis of CRF in the PVN, and stimulates the secretion of ACTH by increasing CRF secretion. This effect on the PVN was mediated, at least in part, via the opioid receptor.

Intravenous beta-endorphin administration fails to alter hypothalamic blood flow in rats expressing normal or reduced nitric oxide synthase activity.

beta-Endorphin (beta-END) significantly contributes to the maintenance of hypothalamic blood flow (HBF) autoregulation during hemorrhagic hypotension in rats. Recently, several natural and synthetic opioid peptides were reported to induce nitric oxide (NO)-mediated dilation in the cerebrovascular bed. In the present study, the effect of beta-END was studied on HBF and hypothalamic vascular resistance (HVR) in vehicle-treated control rats and in rats after the pharmacological inhibition of the NO synthesis by chronic oral application of NG-nitro-L-arginine methyl ester. Intravenous beta-END administration failed to alter HBF or HVR either in control or in NO-blocked animals, and its transient hypotensive effect was not inhibited by NO blockade, indicating that beta-END may not have NO-mediated vasodilator effect in the hypothalamic or in the systemic circulation.

Comparative analysis of effects from prolonged peripheral and intracerebral exposure to β-endorphin

During a long-term (7-day) continuous exposure of rats to β-endorphin from an implanted minipump by the subcutaneous route, changes in their motor activity (stereotypy) and pain sensitivity (hypoalgesia) were similar, though less marked, than those observed during such exposure by the intracerebral route, whereas the change in feeding behavior with the subcutaneous (peripheral) route of β-endorphin administration (hyperphagia) was opposite to that seen with intracerebral administration (hypophagia).

The inhibition of ornithine decarboxylase activity in developing rat tissues by central nervous system β-endorphin is mediated by μ-opioid receptors, but not by δ- or ϵ-opioid receptors

Our laboratory has previously shown that intracerebroventricular (i.c.v.) administration of β-endorphin suppresses brain and liver ornithine decarboxylase activity (ODC; a growth regulatory enzyme) in preweanling rats. This investigation examined, in 6-day-old rats, the relative participation of brain μ-, δ- and ϵ-opioid receptors in β-endorphin's ODC effects, by comparing tissue ODC responses to β-endorphin given alone i.c.v. and in the presence of d-Phe-Cys-Tyr- d-Trp-Orn-Thr-Pen-Thr-NH 2 (CTOP; μ-opioid receptor antagonist), N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174,864; δ-opioid receptor antagonist) or β-endorphin-(1–27) (ϵ-opioid receptor antagonist). Administration of 0.5 μg of β-endorphin alone significantly decreased brain and liver ODC activity 4 h after injection, and the effect was completely blocked by coinjection of CTOP (0.075 μg) but not by ICI-174,864 (0.75 or 3.75 μg) or β-endorphin-(1–27) (3.75 or 7.5 μg). The blockade of endogenous opioid:opioid receptor interactions by either CTOP (at doses > 0.075 μg) or ICI-174,864 alone was accompanied by increased levels of basal ODC activity. The results obtained demonstrate that i.c.v. β-endorphin downregulates ODC expression in central as well as in peripheral tissues by interacting with brain μ-opioid receptors, but not with δ- or ϵ-opioid receptors or μ/δ-opioid receptor complexes. Also, they indicate that endogenous opioid systems have a tonic inhibitory influence on ODC activity which is mediated, at least in part, by μ- and δ-opioid receptors.

Differential ontogenesis of thermal and mechanical antinociception induced by morphine and β-endorphin

The antinociceptive effects induced by β-endorphin and morphine given supraspinally have been previously demonstrated to be mediated by the activation of different neural mechanisms. The present experiments were to examine the effects of intraventricular administration of β-endorphin and morphine in mechanical paw-withdrawal and thermal tail-flick nociceptive tests in rats of 2–28 days of age. 2–4-day-old neonates were not responsive to i.c.v. injection of β-endorphin or morphine for the inhibition of the tail-flick response. The thermal antinociceptive responses induced by β-endorphin and morphine started to develop in 7–14-day-old rats and continued to increase at 21–28 days. The inhibition of the mechanical paw-withdrawal response to β-endorphin was already present in 2-day-old rats and morphine in 4-day-old rats. The mechanical antinociception progressively increased and reached a plateau at 7 days of age for β-endorphin and 28 days of age for morphine. β-Endorphin was found to be more efficacious than morphine in producing mechanical antinociception. The results demonstrate that β-endorphin- and morphine-induced antinociception to mechanical and thermal stimuli develops differently and are consistent with the hypothesis that two descending pain inhibitory systems activated by β-endorphin and morphine are differentially developed.

The β-endorphin inhibition of mitogen-induced splenocytes proliferation is mediated by central and peripheral paracrine/autocrine effects of the opioid

In this study we show that the opioid peptide β-endorphin exerts a tonic inhibitory effect on the proliferative response of splenocytes to the polyclonal mitogen phytohemoagglutinin throughout two separate sites of action: one central and one peripheral. The intracerebroventricular administration of β-endorphin, in fact, induces a significant inhibition of splenocyte proliferation. In contrast, both the intracerebroventricular and the peripheral administration of anti-β-endorphin γ globulins induce a significant increase in proliferation. Moreover, an increase of splenocyte proliferation was observed also after the intravenous administration of γ globulins and intraperitoneal naloxone, and this effect was still present in hypophysectomized rats. The data reported suggest that β-endorphin exerts a tonic inhibitory effect on proliferation, acting centrally, and peripherally throughout a paracrine/autocrine mechanism. FACS experiments show that the effect observed is not the consequence of an alteration of lymphocyte trafficking induced by the opioid.

Central administration of β-endorphin increases food intake in goldfish: pretreatment with the opioid antagonist naloxone

The effect of intraperitoneal or intracerebroventricular β-endorphin administration on food intake has been studied in satiated goldfish. Food intake was evaluated at different time intervals after injections, 0–2, 2–8 and 0–8 h. The 0.1 and 1 μg doses of β-endorphin intracerebroventricularly administered induced an increase in food intake during the first 2 h postinjection, while no modifications on feeding were observed in the next 6 h. These same doses of β-endorphin used increased cumulative food intake at 8 h postinjection. In contrast, intraperitoneal injection of 1 μg of β-endorphin did not modify food intake in any of the studied time intervals. Naloxone, an opioid antagonist, attenuated the β-endorphin-induced feeding increase. These results suggest that opioids may play a role in modulation of feeding central regulation, acting via opioid receptors in goldfish.

Brain cholecystokinin and β-endorphin systems may antagonistically interact to regulate tissue DNA synthesis in rat pups

Previously, we have shown that intracisternal (i.c.) administration of β-endorphin suppresses brain and liver DNA synthesis in rat pups. This finding is consistent with the view that endogeneous CNS β-endorphin plays an important role in controlling postnatal growth. Recent evidence suggests that brain CCK 8, the sulfated carboxyterminal octapeptide fragment of cholecystokinin, may function physiologically as an endogenous opioid antagonist. We now report that CCK 8 injected i.c. together with β-endorphin effectively prevented β-endorphin from inhibiting brain and liver DNA synthesis in 10-day-old rats. CCK 8 blocked the liver DNA effect of β-endorphin via actions within the brain, as subcutaneous administration of CCK 8 was ineffective. In contrast to CCK 8, i.c. administration of CCK 8U (the unsulfated form of CCK 8) together with β-endorphin did not prevent β-endorphin from inhibiting liver DNA synthesis, and only slightly reversed the brain DNA effect. The results obtained support a role for endogenous brain CCK 8 in the modulation of tissue DNA responses to CNS β-endorphin and possibly to other endogenous opioids. If so, interference with brain CCK function could disrupt tissue growth. Thus, normal mammalian development may require a close functional interaction between the cholecystokinin and β-endorphin systems in the brain.

β-Endorphin-stimulated prolactin release in lactating rats following alcohol administration

To delineate the mechanism of alcohol inhibition of the suckling-induced prolactin increase, we examined β-endorphin-stimulated prolactin release in lactating rats separated from their litters. On day 2 of lactation litters were adjusted to eight pups. On day 7, dams were implanted with an atrial catheter; experiments were conducted on lactation day 10. Litters were separated from their dams at 0800. After five hours, a PE50 extension tube filled with heparinized saline was attached to the catheter. At 1400 a preinfusion blood sample was removed and was followed by infusion of saline (control) or alcohol in saline (1.0 and 2.0 g/kg/body weight). Following the removal of a postinfusion blood sample, β-endorphin (600 μg/kg/body weight) was administered. Additional blood samples were withdrawn 10, 30, 60, and 120 min after β-endorphin. Alcohol infusion did not alter basal prolactin. β-Endorphin administration resulted in pronounced prolactin increases in all groups. Alcohol failed to inhibit β-endorphin-induced plasma prolactin increase. From the present study with β-endorphin and our previous studies with sulpiride and thyrotropin-releasing hormone (TRH) it is concluded that the anterior pituitary is not the site where alcohol acts to inhibit suckling-induced prolactin release in rats.

Role of the spinal cord in intracisternal β-endorphin-evoked suppression of liver DNA synthesis in 10-day-old rats

Previously, we have shown that intracisternal (i.c.) administration of β-endorphin (an opioid peptide naturally occurring in the brain) to preweanling rats markedly decreases DNA synthesis (an index of cell proliferation) in both brain and liver. This observation is consistent with our hypothesis that endogenous CNS β-endorphin plays an important role in controlling postnatal growth. The current research specifically undertook to investigate, in 10-day-old rats, whether or not i.c. β-endorphin-evoked suppression of liver DNA synthesis is actually mediated by spinal opioid receptors and/or by descending endorphinergic pathways. In contrast to the i.c. route of administration, β-endorphin given directly into the spinal subarachnoid space via intrathecal (i.t.) injection did not alter liver DNA synthesis, yet was able to evoke profound antinociceptive responses. This demonstrates that intracisternally applied β-endorphin exerts its effect on liver DNA by acting at supraspinal sites, and not by directly stimulating spinal opioid receptors after diffusion from its intracerebral site of injection. As it is possible that β-endorphin's supraspinal actions may activate a descending inhibitory endorphinergic pathway to reduce DNA synthesis, we conducted studies in rat pups administered naloxone intrathecally. Naloxone i.t. was completely ineffective in preventing β-endorphin i.c. from inhibiting liver DNA synthesis. On the other hand, i.t. coinjection of naloxone plus β-endorphin was able to block the analgesic response, while their i.c. coinjection reversed the DNA effect. The results from these studies indicate that opioid systems within the spinal cord do not play a major role in mediating CNS β-endorphin's regulation of DNA synthesis in peripheral tissues. However, the data obtained do not necessarily exclude other spinal neurochemical systems (e.g. adrenergic or serotonergic) from participating in this process.

The inhibition of liver ornithine decarboxylase expression in neonatal rats by maternal separation or CNS β-endorphin is independent of the pituitary

Previously we have shown, in rat pups, that either short-term maternal separation (MS) or central (but not peripheral) administration of β-endorphin (BE) markedly decrease basal levels of ornithine decarboxylase (ODC) activity throughout the body and suppresses liver ODC reponsiveness to injected growth hormone (GH). In this study, hypophysectomized (hypox) pups were used to determine whether the pituitary mediates these effects. Hypophysectomy clearly did not prevent the inhibitory actions of MS or intracisternal (i.c.) BE on liver ODC gene expression. The inability of GH to stimulate ODC activity in hypox animals exposed to MS or given BE i.c. is not due to nutritional deprivation, as glucose supplementation did not reverse the response. The results from these studies demonstrate that the pituitary is not the conduit by which either MS or centrally-administered BE regulates liver ODC activity. Also, they support the hypothesis that BE or an analogous opioid neuropeptide is a prime organizer within the CNS of the adaptive physiological response of neonatal rats to short-term MS. As we have previously shown that autonomic neuronal pathways are not involved in the effects of MS on peripheral tissues, the data obtained suggest that increased activity of this CNS opioid system during MS triggers the release of “neurochemicals” into the bloodstream capable of suppressing growth in the mammalian neonate.

Melatonin counteracts pinealectomy-dependent decreases in rat brain [ 3H]flunitrazepam binding through an opioid mechanism

The effect of intracerebroventricular (i.c.v.) injection of melatonin and/or β-endorphin on the [ 3H]flunitrazepam binding sites in the cerebral cortex of pinealectomized or superior cervical ganglionectomized rats was studied. Pinealectomy decreased the maximum concentration of benzodiazepine receptors ( B max) without affecting the dissociation constant ( K D), while melatonin, ineffective in control animals, counteracted the effect of pinealectomy. Intracerebroventricular injection of β-endorphin increases B max in both control and pinealectomized animals, the effect being significantly higher in the latter. Simultaneous i.c.v. injection of melatonin + β-endorphin did not further increase B max in any group, whereas i.c.v. injection of naloxone significantly blocked the effects of melatonin and/or β-endorphin administration. Pineal sympathetic denervation produced a significant increase in B max and K D, whereas i.c.v. injection of melatonin further increased the former, restoring K D to control values. Neither i.c.v. administration of β-endorphin or melatonin + β-endorphin significantly modified the ganglionectomy-dependent increase in B max, although both treatments restored K D to control values. Naloxone administration had no effect on β-endorphin- and melatonin + β-endorphin-treated ganglionectomized groups, but counteracted the increased effect of melatonin on B max in ganglionectomized animals.

Antinociception from the administration of β-endorphin into the periaqueductal gray of rat is enhanced while that of morphine is inhibited by barbiturate anesthesia

Pentobarbital anesthesia causes about a 10-fold increase in the antinociceptive potency of β-endorphin microinjected into the periaqueductal gray (PAG) region of the rat brain. The antinociceptive response to PAG morphine was markedly attenuated during anesthesia, but returned as the rats regained consciousness. As they recovered from anesthesia, muscular rigidity and body stiffness (catalepsy) also occurred in the pentobarbital treated animals receiving morphine. These results are consistent with the activation of separate and distinct descending pain inhibitory neuronal systems by these two opioid agonists, and the differential modulation of the systems by pentobarbital. They also suggest that the mechanism underlying muscular responses to morphine is sensitive to pentobarbital, and is not shared by β-endorphin.

Effect of Central Administration of β-Endorphin on Lung Ornithine Decarboxylase Activity in Developing Rats

Results from a number of studies suggest a role for endogenous opioids in the regulation of lung development and function. Although it is not known which opioid peptides are involved in these processes, accumulated evidence suggests a prominent role for beta-endorphin (BE). Our study examines the effect of BE on lung ornithine decarboxylase (ODC) activity in preweanling rats. ODC catalyzes the rate-limiting step in the synthesis of the polyamines spermidine and spermine, key regulators of cell growth, multiplication, and differentiation. Central (but not peripheral) administration of BE reduced lung ODC activity by as much as 80% in the 6-d-old rat. Significant decreases in ODC activity were seen at doses of BE as low as 0.5 micrograms/g brain wt. In contrast to the reductions in ODC activity, plasma levels of corticosterone in animals administered BE were approximately five times higher than those seen in control animals. BE's actions on ODC activity and plasma corticosterone levels were prevented by naloxone or naltrexone, indicating that both responses are mediated by opioid receptors. Studies of ODC kinetics showed a profound reduction in Vmax (70% below control values), but no change in Km. The effect was observed only during the first 2 wk of postnatal age, a period of time in lung maturation that is characterized by active alveolarization. Because changes in ODC levels during early postnatal life are associated with perturbations in tissue growth and/or function, the data suggest that CNS BE may influence lung maturation through an indirect action that may involve glucocorticoids.

CNS β-endorphin regulation of insulin-induced ornithine decarboxylase expression in liver of neonatal rats

Previously, we reported that central (but not peripheral) administration of β-endorphin to rat pups decreases basal ornithine decarboxylase (ODC; a growth-associated enzyme) activity throughout the body. This finding is consistent with the view that CNS β-endorphin is an important regulator of postnatal development. Insulin is a hormone that markedly affects liver growth and evidence indicates that this occurs, in part, through its ability to regulate ODC expression. The current study examines the effects of intracisternal injection of β-endorphin on the response of liver ODC to subcutaneous administration of insulin. Insulin (20 IU/kg body wt), markedly increased liver ODC activity in 2-, 4-, 6-, 10-, 18-, and 30-day-old rats. Intracisternal injection of β-endorphin (1.5 μg/g brain wt) inhibited this response to insulin in 2-, 4-, 6-, 10-, and 18-day-old rats, but not in 30-day-old animals. This inhibition by β-endorphin was not reversed by naloxone, indicating that the effect is not mediated by brain μ or δ opioid receptors. Centrally administered β-endorphin also blocked the increases in liver ODC activity evoked by subcutaneous administration of cAMP. The results from these studies suggest that the postulated regulation of postnatal development by CNS β-endorphin may occur through actions on both basal ODC activity and tissue ODC sensitivity to “classical” trophic factors. The modulation by β-endorphin of liver ODC expression apparently occurs distally to cAMP-generating mechanisms