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 effect of acute and chronic nicotine treatment of rats on the mRNA levels coding for the three opioid peptide precursors, for provasopressin and for the alpha 3 subunit of nicotinic receptors in brain, pituitary and/or adrenal medulla of rats was investigated. Nicotine was found to increase the levels of proenkephalin mRNA in the adrenal medulla, but did not affect the levels of PENK mRNA in striatum, hypothalamus and hippocampus. The mRNA levels of prodynorphin were increased together with that of provasopressin in the hypothalamus after nicotine, whereas the prodynorphin mRNA levels in the hippocampus and the striatum remained unchanged. Nicotine treatment resulted in an increase in the pro-opiomelanocortin mRNA levels in the anterior pituitary and in a decrease in the intermediate pituitary, but did not change the levels of pro-opiomelanocortin mRNA in the hypothalamus. The levels of mRNA coding for the alpha 3 subunit of nicotinic receptors in the hypothalamus and the adrenal medulla remained unchanged. The increase in the prodynorphin and provasopressin mRNA levels in the hypothalamus was most pronounced 1 day after s.c. application of two doses of 0.4 mg/kg nicotine (about 100% above control). A smaller increase in mRNA concentrations (about 30%) was found after tonic infusion of the drug for 4 days (4 mg/kg per day), whereas no change was observed after tonic infusion of nicotine for 7 and 14 days indicating the development of complete tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nicotine on mRNA levels encoding opioid peptides, vasopressin and alpha 3 nicotinic receptor subunit in the rat. 152 Oct 36

Peripherally administered nicotine elevates rat plasma adrenocorticotropic hormone (ACTH) levels, acting at brain regions adjacent to or downstream from the third cerebroventricle. Studies evaluated whether the paraventricular nucleus (PVN) mediates directly the ACTH response to nicotine administered i.v. and if regions adjacent to the fourth ventricle (IV) are involved. Direct involvement of the PVN in the release of ACTH in response to i.v. nicotine (0.03 or 0.01 mg/kg b.wt.) was refuted by studies in which the administration of the nicotinic cholinergic antagonist, mecamylamine (20 or 40 micrograms bilaterally adjacent to the PVN), failed to block ACTH secretion. To activate sites distal to the third ventricle, nicotine (0.25, 0.5, 2.5 or 5.0 micrograms) was injected into the IV; ACTH levels peaked between 3 and 7 min. Nicotine 0.25 micrograms injected into the IV elevated ACTH to levels within the range of those produced by i.v. nicotine (0.03 mg/kg b.wt.). To confirm that sites accessible from the IV are involved, mecamylamine was administered i.v. (0.5 or 1.0 mg/kg b.wt.) or into the IV (4 or 40 micrograms) and nicotine was delivered by the opposite route. Intravenous mecamylamine reduced the plasma ACTH response to 0.25 micrograms of nicotine in the IV. Mecamylamine, administered into the IV before i.v. nicotine (0.03 mg/kg b.wt.) antagonized the effect of nicotine. These results indicate that stimulation of ACTH secretion by nicotine delivered i.v. occurs via structures accessible from the IV. In contrast to prevailing ideas, the PVN does not appear to be the direct site of action of nicotine.
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PMID:Role of the fourth cerebroventricle in mediating rat plasma ACTH responses to intravenous nicotine. 215 57

Using specific ligands, we find that lung cancer cell lines of diverse histologic types express multiple, high-affinity (Kd = 10(-9)-10(-10) M) membrane receptors for mu, delta, and kappa opioid agonists and for nicotine and alpha-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations (approximately 100 nM) found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas mu, delta, and kappa opioid agonists at low concentrations (1-100 nM) inhibited lung cancer growth in vitro. We also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides (beta-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, we tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a "tumor suppressor" system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.
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PMID:Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines. 215 43

In the first experiment a conditioned taste aversion paradigm was used to characterize a dose-response curve for the aversive properties of nicotine in male Sprague-Dawley rats. Doses of nicotine ranging from 0.01 to 0.46 mg/kg, 2.0 ml of 0.47 M lithium chloride, or saline were injected, ip, 10 min after exposure to a novel saccharin solution. Amount of saccharin consumed in a two-bottle test was assessed 72 h later. Nicotine doses of 0.046 mg/kg and above produced a significant degree of conditioned taste aversion. In a second experiment, four groups of 10 rats each were injected with saline, 0.022 mg/kg nicotine, 0.46 mg/kg nicotine, or 2.0 ml 0.47 of M LiCl. Doses of 0.46 mg/kg nicotine and 0.47 M LiCl elevated plasma beta-endorphin concentrations significantly above saline control values. The 0.022 mg/kg dose, the highest dose that did not produce conditioned taste aversion in Experiment 1, did not significantly increase plasma beta-endorphin concentrations. This finding suggests that doses of nicotine that produce conditioned taste aversion also promote the release of pituitary stress hormones. Taken together these data suggest that some of the pharmacological and behavioral effects attributed to nicotine, including the release of endogenous neuromodulators, may be dose-dependent concomitants of the aversive effects of nicotine in nicotine-naive animals.
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PMID:Characterization of a dose-response curve for nicotine-induced conditioned taste aversion in rats: relationship to elevation of plasma beta-endorphin concentration. 216 51

The literature on corticotropin (ACTH) regulation of cortisol secretion, effects of nicotine on plasma cortisol and ACTH levels, and the cortisol response to smoking cessation is reviewed. A dose-dependent increase in plasma cortisol levels is found in habitual smokers after smoking two cigarettes. Nicotine mediates this response via a central mechanism to release cortisol from the adrenal cortex. The sites of action of nicotine appear to be in the hypothalamus or brain stem. Complete cessation of smoking is followed by a fall in plasma cortisol levels that is associated with the withdrawal of the nicotine stimulus. In addition, anxiety levels increase and plasma epinephrine levels decrease. Nicotine withdrawal symptoms confront smokers who want to quit. Many of the symptoms seem to be related to the body's response to changes in cortisol levels. As part of a comprehensive smoking cessation program, one or two intramuscular injections of ACTH gel have been shown to help smokers stop and continue to abstain from smoking.
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PMID:Nicotine, corticotropin, and smoking withdrawal symptoms: literature review and implications for successful control of nicotine addiction. 255 98

Nicotine is a potent secretagogue for the release of adrenocorticotropin (ACTH) from the anterior pituitary in vivo. However, the location of its action is unknown; knowledge of this is essential for elucidating its mechanism. Our studies show that cytisine, a peripherally acting nicotinic cholinergic agonist, given i.v. at doses equimolar or greater than nicotine, failed to elevate plasma ACTH levels, whereas nicotine (0.01 and 0.03 mg/kg b.wt.) had significant effects. Nicotine (10(-7)-10(-4) M) had no effect on the secretion of beta-endorphin by anterior pituicytes in vitro, nor did it potentiate the action of corticotropin-releasing factor (10(-9) or 10(-8) M). Intracerebroventricular injection of nicotine (1-20 micrograms) significantly elevated ACTH levels. Moreover, ACTH responses to nicotine delivered into the hypothalamic region of the third ventricle were significantly greater than those elicited by injection into the upper region. Additional studies were conducted to determine the earliest age at which nicotine stimulates ACTH. The response to i.p. nicotine (1 or 2 mg/kg b.wt.) was present but diminished during the postnatal period, whereas maximal responses comparable to mature rats were attained by day 15. To establish whether nicotine has a central effect in younger animals, nicotinic antagonists were tested. Hexamethonium (2 mg/kg b.wt.), a peripherally acting antagonist, was ineffective against nicotine (0.025 and 2.0 mg/kg b.wt.), whereas mecamylamine (2 mg/kg b.wt.), inhibitory at both peripheral and central sites, blocked the ACTH response. Thus, whether administered peripherally or centrally, nicotine activates central mechanisms mediating the release of ACTH; it appears that the target(s) for nicotine are within the hypothalamus or brainstem.
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PMID:Nicotine elevates rat plasma ACTH by a central mechanism. 282 98

The effects of nicotine on secretion of the pituitary peptides beta-endorphin, alpha MSH, and ACTH were studied using the isolated perfused mouse brain (IPMB) and isolated superfused pituitaries of C3H mice. Nicotine (6.1 microM) stimulated secretion of beta-endorphin immunoreactivity from C3H IPMB approximately twofold. Secretion of alpha MSH immunoreactivity was stimulated approximately two- and sixfold by 6.1 microM and 12.2 microM nicotine, respectively. However, nicotine (6.1 microM) had no direct effect on the secretion of beta-endorphin, alpha MSH, or ACTH immunoreactivities from the isolated superfused pituitaries. The data suggest nicotine acts in the brain to stimulate pituitary secretion of alpha MSH and beta-endorphin. Electrocorticographic (ECoG) activity of the IPMB was monitored. Nicotine induced characteristic ECoG changes including a reduction of input voltage, a biphasic response of rapid desynchronization followed by prolonged synchronization, and seizure at high doses (12.2 microM).
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PMID:Effects of nicotine on beta-endorphin, alpha MSH, and ACTH secretion by isolated perfused mouse brains and pituitary glands, in vitro. 298 5

We studied the secretion and tissue contents of adrenorphin in human pheochromocytomas. In 17 human pheochromocytomas from 11 patients, we found a remarkably wide distribution in immunoreactive adrenorphin levels (3-7771 pg/mg tissue). Adrenomedullary pheochromocytomas contained a significantly larger amount of immunoreactive adrenorphin (2295 +/- 1092 pg/mg, mean +/- SE) than did extramedullary ones (17.8 +/- 8.4 pg/mg). Gel chromatographic studies revealed that immunoreactive adrenorphin consisted largely of material emerging at the position of synthetic adrenorphin in both pheochromocytoma and normal adrenal medulla tissue. Nicotine (10(-5) M) significantly stimulated the secretion of immunoreactive adrenorphin as well as catecholamines from cultured human pheochromocytoma cells. Adrenorphin was a more potent inhibitor of catecholamine secretion evoked by 10(-5) M nicotine than was met-enkephalin in cultured human pheochromocytoma cells. The 50% inhibitory concentrations (IC50) were 1.1 X 10(-6) and 6.5 X 10(-5) M for adrenorphin and met-enkephalin, respectively. The effect of adrenorphin was much the same as that of dynorphin-(1-13) (IC50, 1.0 X 10(-6) M) and BAM-12P (IC50, 4.5 X 10(-6) M). These results indicate the presence and secretion of adrenorphin in human pheochromocytomas. Adrenorphin may play an important role in regulating catecholamine secretion in human pheochromocytoma.
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PMID:Studies on adrenorphin in pheochromocytoma. 381 99

Nicotine is known to release neuroendocrine substances which may subsequently reinforce smoking behavior by improving mood states. The purpose of this study was to examine changes in plasma beta-endorphin and mood states during periods of chronic smoking, abstinence from smoking, and abstinence while chewing nicotine gum. A modified A-B-A-C design was used. Normal male volunteers were randomly assigned to an experimental or control group. Over a 12-day protocol, experimental subjects smoked ad libitum for 2 days, were abstinent for 4 days, resumed smoking for 2 days, and then chewed nicotine gum for the final 4 days. Control subjects smoked ad libitum throughout the entire protocol. Results indicated that changes in plasma beta-endorphin levels were not related to changes in the four smoking conditions. Plasma nicotine and mood states were related, such that dysphoric moods increased during abstinence from smoking in comparison to the control group. To investigate further the relationships between nicotine, beta-endorphin and reinforcement for smoking, it may be necessary to characterize endogenous opioid peptide release in the central nervous system during smoking.
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PMID:Plasma nicotine, plasma beta-endorphin and mood states during periods of chronic smoking, abstinence and nicotine replacement. 786 39

Classical nicotinic receptors are neurotransmitter-gated channels that, upon activation by acetylcholine, induce the opening of an intrinsic cationic channel. We have recently observed that, in frog pituitary melanotrophs, nicotine stimulates alpha-melanocyte-stimulating hormone (alpha-MSH) release through a noncholinergic mechanism. In the study reported here, we investigated the intracellular events that mediate the response of frog melanotrophs to nicotine. Nicotine was capable of stimulating alpha-MSH release in the absence of Ca2+ and/or Na+ in the extracellular medium. A short pulse of nicotine induced a rapid and transient increase of cytosolic free Ca2+ concentration ([Ca2+]i). The effect of nicotine on Ca2+ mobilization was not affected in the absence of Na+ and Ca2+ in the extracellular medium, indicating that the nicotine-evoked increase in [Ca2+]i did not result from Na+ or Ca2+ influx. Nicotine induced both an increase in inositol trisphosphate and a reduction in phosphaditylinositol bisphosphate concentrations but did not affect cAMP production. The present results indicate that nicotine-induced stimulation of alpha-MSH release in frog melanotrophs can be explained by activation of inositolphospholipid breakdown and mobilization of inositol triphosphate-dependent intracellular Ca2+ pools. These data provide evidence for the existence of an unusual type of noncholinergic nicotine receptor positively coupled to phospholipase C.
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PMID:Functional characterization of a nonclassical nicotine receptor associated with inositolphospholipid breakdown and mobilization of intracellular calcium pools. 1657 48


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