Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 2 weeks of lithium carbonate administration at therapeutic plasma levels were examined in 11 normal volunteers. Serotoninergic function before and after lithium administration was assessed using low-dose intravenous clomipramine hydrochloride challenge, while urinary and plasma metabolites of norepinephrine (NE) were used to assess noradrenergic systems. Long-term lithium administration in normal subjects did not significantly or consistently enhance serotonin-mediated neuroendocrine responses but did increase measures related to neuronal release of NE. No statistically significant effects of lithium on prolactin, corticotropin, or cortisol responses to serotoninergic challenge could be detected. The probability of a type II error was assessed, and a doubling of prolactin level was unlikely to have been missed, although more modest increases (less than 75%) could have been overlooked. After 2 weeks of lithium administration, there were significant increases in 24-hour urinary excretion of NE, normetanephrine, and fractional NE release, compatible with increased neuronal release of NE and a lithium-induced subsensitivity in alpha 2-adrenergic receptor function. These changes were not statistically significant after 1 week of administration, suggesting that increased NE release is characteristic of long- rather than short-term lithium administration. Since previous reports have demonstrated enhanced prolactin responses after short- but not long-term lithium use, the present study points to temporal specificity in lithium's effects on both serotoninergic and noradrenergic function. Lithium's effects on NE release were consistent but small (a 16% increase), while its effects on serotoninergic responses were larger (a 50% increase in prolactin responses) but quite inconsistent, suggesting that neither of these systems is the primary site of action of lithium.
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PMID:The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects. 842 26

The effect of both chronic and acute lithium treatment on hypothalamic opioid peptides was investigated. Acute treatment with lithium was found to stimulate the release of beta-endorphin, dynorphin and Met-enkephalin from perfused rat hypothalamic slices. Application of tetrodotoxin was found to have no effect upon the stimulation indicating it to be mediated at the nerve terminal level. The release of hypothalamic opioid peptides is known to be under the chronic control of a system of inhibitory autoreceptors. Blockade of these autoreceptors with, for example, the opioid receptor antagonist naloxone causes a release of all three opioid peptides. Simultaneous addition of naloxone and lithium was found to have no additive effect on the release of any opioid, suggesting lithium acts via an inhibition of the inhibitory autoreceptor. Preincubation with pertussis toxin prevented the lithium stimulation of dynorphin and Met-enkephalin, but not beta-endorphin, release, indicating lithium interacts with a G-protein to affect the autoreceptor controlling the release of dynorphin and Met-enkephalin. Chronic treatment with lithium in vivo (10 days) had no effect on the basal release or hypothalamic content of any of the opioids, but prevented the naloxone-stimulated release of dynorphin and Met-enkephalin in vitro. Long-term treatment with lithium would thus appear to inactivate the autoreceptor(s) controlling their release. These data demonstrate a lithium-stimulated release of hypothalamic beta-endorphin, Met-enkephalin and dynorphin, apparently mediated via an inhibition of the autoreceptors controlling their release. Chronic treatment with lithium permanently inactivated the autoreceptor(s) controlling the release of dynorphin and Met-enkephalin but not beta-endorphin. Lithium would appear to mediate its effects upon Met-enkephalin and dynorphin release via an interaction with a pertussis toxin-sensitive G-protein. The mechanisms underlying its release of beta-endorphin are at present uncertain.
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PMID:Stimulation of hypothalamic opioid peptide release by lithium is mediated by opioid autoreceptors: evidence from a combined in vitro, ex vivo study. 217 62

Lithium stimulated corticotropin (ACTH) secretion by mouse pituitary tumor cells (AtT-20/D16-16) and by normal rat anterior pituitary cells in primary culture. Effects were observed at less than 2 mM LiCl. ACTH secretion was comparable in magnitude to that induced by other secretagogues, was calcium dependent, and was inhibited by somatostatin. Lithium also induced changes in [3H]inositide metabolism; these changes accompanied and were correlated with changes in ACTH secretion. The most prominent and reliable effect was to increase [3H]inositol monophosphate. Other secretagogues had no effect on [3H]inositides in the presence or absence of lithium. Pretreatment with lithium for 3 hr desensitized the cells to the effects of subsequent exposure to lithium. The cells were not desensitized to lithium by pretreatment with other secretagogues, nor were they desensitized by lithium to the effects of corticotropin-releasing factor, high potassium, or forskolin. However, pretreatment with lithium did desensitize the cells to stimulation by phorbol esters. The interaction between lithium and phorbol esters suggests the involvement of inositide metabolism and protein kinase C in the regulation of ACTH secretion and possibly of other hormones or neurotransmitters. It also suggests new avenues of research into the basis of lithium's psychopharmacological effects.
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PMID:Lithium induces corticotropin secretion and desensitization in cultured anterior pituitary cells. 298 36

The effects of lithium on the activity of adenylate cyclase stimulated by hormones, which act via the stimulatory guanine nucleotide binding subunit (Ns), by forskolin, which acts at the catalytic subunit, and by guanyl-5'-yl imidodiphosphate (GppNHp), which locks the enzyme into a permanently active state, have been compared in a preparation of membranes from the cerebral cortex of the rat. Lithium ions (Li+) in vitro at 2-4 mM inhibited cyclase stimulated by isoproterenol and forskolin, but had no effect on the inhibition induced by met-enkephalin of the enzyme stimulated by forskolin, mediated by the inhibitory guanine nucleotide binding subunit (Ni). Inhibition of the activity stimulated by forskolin and GppNHp was competitive with magnesium (Mg++). In a preparation of slices of cerebral cortex Li+ at 1-2 mM inhibited accumulation of cyclic AMP stimulated by forskolin in a non-competitive manner. In a preparation of membranes from the caudate nucleus, Li+ at 2-4 mM inhibited dopamine-stimulated adenylate cyclase, but this effect was not observed in the presence of additional sodium (Na+). Membranes prepared from animals fed with Li+ to give a mean serum level of 0.52 mM and a mean brain level of 1.32 mM, showed a reduced response to manganese (Mn++), forskolin, isoproterenol and GppNHp in the cerebral cortex, but no change in the degree of activation of the enzyme by either dopamine or forskolin, or the degree of inhibition by met-enkephalin, in the caudate nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of lithium in vitro and ex vivo on components of the adenylate cyclase system in membranes from the cerebral cortex of the rat. 303 12

Interactions among lithium, calcium, and phorbol esters in the regulation of adrenocorticotropin hormone (ACTH) release were examined in a tumor cell line (AtT-20) of the anterior pituitary. Lithium, which blocks the phosphatase that converts inositol phosphates (IPs) to inositol, increases the levels of IPs in these cells and stimulates ACTH release. This ion potentiates the ability of calcium, an activator of phospholipase C, to raise levels of IPs in these cells and to stimulate ACTH secretion. Pretreatment of AtT-20 cells with calcium specifically abolishes the ACTH release response to lithium or calcium, a result suggesting that these secretagogues may act through a common mechanism to induce hormone secretion. Prior exposure of AtT-20 cells to either lithium or calcium also attenuates the ACTH release induced by phorbol ester, an activator of protein kinase C. To examine the link among lithium, calcium, phosphatidylinositol (PI) turnover, and phorbol ester-evoked ACTH secretion, AtT-20 cells were treated with 1-oleoyl-2-acetoyl-sn-3-glycerol (OAG), an analogue of the diacylgylcerols that are formed by phospholipase C during PI metabolism and that also activate protein kinase C. OAG itself does not alter ACTH release or the levels of IPs in AtT-20 cells. Pretreatment of AtT-20 cells with OAG, however, selectively blocks the ACTH release response to lithium, calcium, or phorbol ester. Furthermore, such pretreatment reduced the ability of lithium to increase levels of IPs. The results suggest that one mechanism of action of lithium is to potentiate selectively an action of calcium, possibly the stimulation of phospholipase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions among lithium, calcium, diacylglycerides, and phorbol esters in the regulation of adrenocorticotropin hormone release from AtT-20 cells. 303 56

Effects of lithium and rubidium administered into the cerebral ventricles of conscious cats on psychomotor excitation produced by synthetic human beta-endorphin similarly injected have been investigated. Lithium, but not rubidium, prevented the psychomotor stimulation caused by beta-endorphin. Naloxone, applied intracerebroventricularly, also prevented the psychomotor stimulation produced by this polypeptide. It appears, therefore, that only lithium has a psychotherapeutic value when homeostatic neurohumoral mechanisms are disturbed in the central nervous system by a surplus of beta-endorphin.
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PMID:[Psychomotor excitation caused by beta-endorphin: effect of rubidium and lithium]. 609 49

Chronic lithium administration significantly changes characteristics of the circadian rhythms in rat brain alpha- and beta-adrenergic, muscarinic acetylcholine, dopamine, opiate, and benzodiazepine receptors. There are changes in the timing of the peak number of receptors (phase-position), in the amplitude of the rhythms, and in the 24-hour mean number of receptors. The circadian rhythm in the number of forebrain alpha- and beta-adrenergic and benzodiazepine receptors is abolished. The phase-position of forebrain acetylcholine and opiate receptors and striatal benzodiazepine receptors is delayed. As the rhythms of the dopamine receptor number and alpha-melanocyte-stimulating hormone secretion become bimodal, their phase positions are difficult to evaluate. The mean number of forebrain alpha- and beta-adrenergic, acetylcholine, opiate, and striatal benzodiazepine receptors increases. The mean number of forebrain benzodiazepine and striatal dopamine receptors and the mean concentration of alpha-melanocyte-stimulating hormone decreases. Lithium has profound effects on each of the receptor rhythms measured. Slowing and altering circadian rhythms may contribute to the therapeutic effects of chronic lithium treatment in affective disorders.
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PMID:Effect of lithium on circadian neurotransmitter receptor rhythms. 612 Apr 79

We investigated the effect of lithium on prolactin (PRL) secretion in both urethane-anesthetized rats and right atrial catheter-bearing conscious rats. Basal plasma PRL levels were not significantly altered for 4 h after lithium administration. However, lithium treatment apparently potentiated PRL release by haloperidol in both conscious and urethane-anesthetized rats. In addition, the inhibition by apomorphine of PRL secretion was significantly antagonized by lithium in conscious rats. Lithium had no effect on the enhancement of PRL secretion by either 5-hydroxytryptophan or beta-endorphin in conscious rats. These observations indicate that lithium affects PRL secretion when dopaminergic neural activity is altered. Therefore, it is possible to postulate that the decrease of dopamine receptor sensitivity by lithium may be related to the therapeutic action of the drug on affective disorders.
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PMID:Inhibition by lithium of dopamine receptors in rat prolactin release. 626 3

We examined the effects of adrenocorticotropic hormone (ACTH) on the immobilization of rats in the forced swim test with the administration of imipramine, desipramine, or lithium. A single administration of either imipramine (10-30 mg/kg, i.p.) or desipramine (30 mg/kg, i.p.) significantly decreased the duration of immobility in normal rats in a dose-dependent manner. Lithium (10-100 mg/kg, p.o.), however, had no affect on the performance of rats in the forced swim test. ACTH (100 microg/day), administered subcutaneously to rats for 1, 3, 7, and 14 days, had no apparent effect on the duration of immobility in this test. The immobility-decreasing effect induced by a single administration of either imipramine (10-30 mg/kg, i.p.) or desipramine (30 mg/kg, i.p.) was blocked by chronic administration of ACTH for 3-14 days. The reduction of immobility, induced by chronic administration of imipramine (10 mg/kg, i.p.) for 15 days, was blocked by treatment with ACTH for 14 days. When lithium (100 mg/kg, p.o.) was administered for 15 days concurrently with imipramine (10 mg/kg, i.p.), we observed a significant decrease in immobility in rats treated with ACTH for 14 days. We suggest that chronic treatment of rats with ACTH may prove to be an effective model of tricyclic antidepressants-treatment-resistant depression.
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PMID:Influence of ACTH on the effects of imipramine, desipramine and lithium on duration of immobility of rats in the forced swim test. 1181 8

Experiences of early life stress are more prevalent among depressed patients than healthy controls. Neuropeptide Y (NPY) was suggested to play a role in the pathophysiology of depression. Consequently, we investigated in adult rats the effects of maternal deprivation for 3 h/day during postnatal days (PND) 2-14 and of dietary lithium during PND 50-83 on brain levels of NPY-like immunoreactivity (LI). Brain levels of corticotropin-releasing hormone (CRH) and serum corticosterone were also measured. Maternal deprivation reduced NPY-LI levels in the hippocampus and the striatum but increased NPY-LI and CRH-LI levels in the hypothalamus. Lithium treatment counteracted the effect of maternal deprivation in the hippocampus and striatum by increasing NPY-LI levels. In the hypothalamus, lithium tended to decrease CRH-LI but further increased levels of NPY-LI; it also increased serum corticosterone levels. The results suggest that early life stress has long-term effects on brain NPY with implications for the development of depression/vulnerability to stress, and that one therapeutic mechanism of action of lithium is to increase brain NPY.
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PMID:Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes. 1243 50


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