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)

A number of studies have indicated a relationship between brain peptide activity and sensitivity to the behavioral effects of ethanol. Specifically, it has been suggested that ethanol effects are mediated by changes in the endogenous opioid peptides derived from the proopiomelanocortin (POMC) precursor. Most cell bodies containing brain POMC-derived peptides are found in the arcuate nucleus of the hypothalamus. Neonatal administration of monosodium glutamate (MSG) has been reported to destroy cell bodies of the arcuate nucleus. We treated WSC strain mice on postnatal Day 4 with a single SC injection of 4 mg/g MSG or saline. When adult, MSG and control mice were challenged with an IP injection of ethanol and its effect on body temperature, open field activity, or duration of loss of righting reflex was assessed. Blood ethanol concentration (BEC) was measured and the hypothalamic content of beta-endorphin like immunoreactivity (beta-EP) was determined by radioimmunoassay. beta-EP was markedly reduced in both females and males by MSG treatment. MSG-treated animals of both sexes showed significantly less ethanol-induced hypothermia than controls. BEC was higher in MSG-treated animals of both sexes than in controls, so the differences were not due to ethanol pharmacokinetics. beta-EP was generally lower in males. Duration of righting reflex was prolonged in MSG treated animals, and the reduction in open field activity was potentiated. These latter effects may be in part attributable to the higher BECs achieved in lesioned animals. These data suggest that beta-EP cell bodies in the arcuate nucleus of the hypothalamus mediate neurosensitivity to some effects of ethanol in mice, but further experiments will be necessary to implicate beta-EP specifically.
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PMID:Neonatal monosodium glutamate lesions alter neurosensitivity to ethanol in adult mice. 294 68

Oxytocin (OXY) administered intracisternally to adult male mice produced a significant dose-related (1-4 micrograms) increase in colonic temperatures at an ambient temperature of 25 degrees C. The maximal rise in temperature occurred 30 min after administration of the peptide. The interactive effects on colonic temperature of central OXY with equimolar amounts of neurotensin, bombesin or beta-endorphin or of 2 2 mg/kg of chlorpromazine were investigated. OXY significantly antagonized the hypothermia produced by all of these substances. Pretreatment of mice with haloperidol or naloxone failed to prevent OXY-induced hyperthermia. The hyperthermic action of OXY and the interactive effects of OXY with other peptides on thermoregulation may be physiologically significant during parturition and lactation.
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PMID:Interactive effects of intracisternal oxytocin and other centrally active substances on colonic temperatures of mice. 294 25

Neurotensin (NT) differentially altered ethanol-induced anesthesia as measured by duration of loss of righting response or by blood ethanol levels producing loss of righting response in mice (LS and SS) which were selectively bred for differences in response to ethanol. At doses of 5-500 ng i.c.v., NT increased ethanol sensitivity in SS mice, but not in LS mice, as measured by blood ethanol concentrations at loss of righting response. At higher doses, 0.5-10 micrograms i.c.v., NT enhanced the sensitivity of both SS and LS mice to ethanol-induced anesthesia. The hypothermic effect of ethanol determined at loss of righting response was not altered in either LS or SS mice at low doses of NT, but at higher doses NT enhanced ethanol-induced hypothermia in both lines of mice. The altered anesthetic sensitivity was specific for ethanol in that NT did not alter pentobarbital-induced sleep time in either LS or SS mice and halothane anesthesia was altered slightly only in LS mice. NT analogues, N-acetyl-NT8-13, and [D-Trp11]-NT but not NT1-8 enhanced the anesthetic action of ethanol in SS mice. Bombesin, cholecystokinin sulfate, substance P, [D-Trp8, D-Cys14]-somatostatin and corticotropin releasing hormone (CRF) were not effective in enhancing ethanol-induced anesthesia in LS or SS mice. CRF appeared to decrease ethanol sensitivity in LS but not in SS mice. Beta-Endorphin (beta-END) markedly increased the ethanol sensitivity of SS and to a lesser extent of LS mice at relatively high doses, e.g. 0.5-1.0 micrograms i.c.v. The results of the present study indicate that differences in brain sensitivity of LS and SS mice to ethanol may be mediated by genetic differences in NT systems. Likewise, NT, and probably beta-endorphin, may interact with other neurochemical processes that are involved in the mechanism of ethanol-induced anesthesia and that differ genetically in LS and SS mice.
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PMID:Neurotensin selectively alters ethanol-induced anesthesia in LS/Ibg and SS/Ibg lines of mice. 294 96

The effects of beta-endorphin and beta-endorphin-(1-27) on the body temperature of mice was studied at an ambient temperature of 10 degrees C. Intracerebroventricular injection of beta-endorphin (0.25-4 micrograms) and beta-endorphin-(1-27) (0.61 to 10 micrograms) caused a dose-related hypothermia. The duration of hypothermia induced by beta-endorphin-(1-27) was shorter than that induced by beta-endorphin. The hypothermia induced by 2 micrograms of beta-endorphin was attenuated by 5 micrograms of beta-endorphin-(1-27). Our results indicated that beta-endorphin-(1-27) is a partial agonist which produces a small degree of hypothermia and an antagonist which blocks the beta-endorphin-induced hypothermia.
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PMID:Beta-endorphin-(1-27) antagonizes beta-endorphin-induced hypothermia in mice. 295 45

Little is known about adrenocortical function after coronary bypass surgery in which moderate to deep hypothermia and cardiopulmonary bypass are used particularly with intraoperative steroid administration. Therefore, we performed a pilot study in which immediately preoperative and 18-hour postoperative serum cortisol levels were determined in eight patients who received 1.0 to 1.5 gm of methylprednisolone intravenously during surgery; postoperative serum cortisol (3 +/- 1 microgram%) levels were lower than preoperative levels (15 +/- 3 microgram%, p less than 0.05). To determine the possible cause of these striking findings, the effects of moderate to profound hypothermia and cardiopulmonary bypass upon adrenocortical functioning were investigated without the influence of intraoperative steroid administration. Serum cortisol and aldosterone levels and their response to adrenocorticotropic hormone (ACTH) (Cortrosyn) were determined before coronary bypass surgery and at various postoperative intervals in seven patients. Postoperative cortisol and aldosterone levels increased markedly over their preoperative values, reaching a maximum at 6 to 12 hours (cortisol 16 +/- 8 vs 63 +/- 23 micrograms%, p less than 0.05, aldosterone 15 +/- 5 vs 51 +/- 22 ng%, p less than 0.05). Adrenal response to ACTH was normal preoperatively, during rewarming from hypothermia, and 18 hours, and 7 days postoperatively. In summary, normal adrenal responsiveness occurs after coronary bypass surgery, in spite of hypothermic cardiopulmonary bypass and the effects of anesthesia, and a single dose of methylprednisolone during surgery is associated with markedly lower serum cortisol levels and prevents the usual adrenal stress response to bypass surgery for at least 18 hours postoperatively.
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PMID:Adrenal function following coronary bypass surgery. 299 Jan 87

Peripheral treatment with adrenocorticotropin (1-24) (ACTH1-24), at different doses and sequences, consistently antagonized the decrease in body temperature produced by morphine in the freely moving guinea pig, whereas adrenocorticotropin (4-10) (ACTH4-10), which lacks corticotrophic activity, was partially effective only when it was administered in a high dose 24 h prior to morphine. Centrally administered ACTH1-24 completely prevented the hypothermic effect of intracerebroventricularly (i.c.v.)-injected morphine. Likewise, the i.c.v. administration of ACTH4-10 was equally effective in blocking the i.c.v. morphine-induced hypothermia. Neither ACTH1-24 nor ACTH4-10 did produce changes in body temperature. These results suggest that peripherally administered ACTH1-24 antagonizes indirectly the actions of morphine through the release of adrenal corticosteroids, whereas centrally injected ACTH1-24 or ACTH4-10 act as direct antagonists of morphine effects through opioid receptors.
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PMID:Effect of ACTH-like peptides on morphine-induced hypothermia in unrestrained guinea pigs. 301 68

After injection of 5 micrograms into a lateral cerebral ventricle, 6 of 12 peptides induced mean changes of 0.3 degree C or more in rectal temperature of rabbits. When beta-endorphin was studied further with 1.25-5 micrograms in 10, 23 and 30 degrees C environments, it induced dose-related hypothermia in the cold, hyperthermia in the heat and progressively smaller increases in body temperature with increasing doses at 23 degrees C.
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PMID:Altered body temperature of rabbits after central injection of beta-endorphin and other peptides. 315 76

alpha-MSH within the septal region of the brain has been implicated in fever control; this peptide and ACTH (1-24), which contains the alpha-MSH amino acid sequence, reduce fever when given intracerebroventricularly (ICV) or peripherally. These peptides also cause hypothermia when given in doses larger than those required to reduce fever. Both peptides occur naturally within the preoptic PO region of the brain, the CNS locus of primary temperature control. alpha-MSH (350 ng) injected bilaterally into the PO region via chronic cannulas reduced fever caused in six rabbits by IV injection of IL-1 (interleukin 1, endogenous or leukocyte pyrogen) but had no effect in afebrile animals. A larger dose (1.5 micrograms) not only reduced fever but caused hypothermia in 12 rabbits. In separate experiments PO injections of ACTH (1-24) (1 microgram) reduced normal temperature. In the same six rabbits alpha-MSH (1 microgram) caused slightly smaller hypothermia. alpha-MSH (1.5 micrograms) also had no effect in 8 afebrile rabbits when injected into the septum. The primary conclusion is that alpha-MSH receptors within the PO region can contribute to both the antipyretic and hypothermic actions that are observed after ICV and peripheral administration of the peptide.
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PMID:Effects of preoptic microinjections of alpha-MSH on fever and normal temperature control in rabbits. 360 19

[Nle4,D-Phe7]-alpha-MSH has exceptional potency in certain biological assays of alpha-MSH activity such as skin darkening in frogs. However, this analog was equipotent to alpha-MSH in induction of grooming in the rat and had opposite effects on the performance of a visual discrimination task. These results led to the suggestion that distinct differences may exist between the melanocyte and CNS receptors for alpha-MSH. We determined the antipyretic and hypothermic potencies of centrally and peripherally administered [Nle4,D-Phe7]-alpha-MSH, relative to those of alpha-MSH, in the rabbit. Central injections of 40 and 80 ng of [Nle4,D-Phe7]-alpha-MSH caused hypothermia in afebrile rabbits, whereas 20 and 10 ng, which had no effect on afebrile body temperature, caused greater than 40% reduction in leukocytic pyrogen-induced fever. These results indicate that this analog is approximately 10 times more potent in reducing fever than alpha-MSH, making it the most potent antipyretic substance yet described. In contrast, IV administration of 16 micrograms of the analog, an extremely large dose relative to established antipyretic doses of alpha-MSH, elicited weak, variable responses. Since this analog is said to be resistant to degradation by serum enzymes, the contrast between the effects of central and peripheral administration may reflect a limited ability of the analog to cross the blood brain barrier when given IV. Our results do not suggest any distinct differences between the melanocyte receptors for alpha-MSH and those involved with CNS control of temperature. The marked central potency of [Nle4,D-Phe7]-alpha-MSH could result from an increased duration of action and/or a greater affinity for central receptor sites relative to alpha-MSH.
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PMID:Antipyretic activity of a potent alpha-MSH analog. 387 37

alpha-MSH reduces fever in rabbits when administered IV, ICV, or by gavage; however, the applicability of this finding to higher species, specifically to primates, has not been determined. In this study, we chose the squirrel monkey as an appropriate primate model since it responds reliably to peripheral administration of bacterial endotoxins that cause fever in man. From pilot studies, doses of S. typhosa endotoxin necessary to produce maximum fever and doses of alpha-MSH which did not cause hypothermia were determined for each animal. In the main experiments endotoxin was given via an indwelling catheter in the saphenous vein, followed by alpha-MSH injections when the rectal temperature increased 0.3 degrees C. alpha-MSH (100-400 micrograms) reduced the area under the fever curve an average of 50.0%, but had no effect on afebrile temperature. Molar equivalent amounts of the antipyretic drug acetaminophen had little effect on fever. These findings support the idea, based on research on rabbits, that alpha-MSH has a role in central modulation of fever.
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PMID:Intravenous alpha-MSH reduces fever in the squirrel monkey. 387 18


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