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

Alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) possess properties suggesting that they may be involved in the pathogenesis of restless legs syndrome (RLS). We sought to determine if alpha-MSH and ACTH when administered centrally in rat recapitulate features reminiscent of RLS: increased activity, sleep fragmentation, and periodic movements during sleep. Rats were instrumented with electroencephalography, electromyography, and intracerebral cannulae and recorded for the measurement of sleep, periodic movements, and behavior following intracerebroventricular administration of alpha-MSH, ACTH, or saline. Studied behavior included grooming, locomotion, and rearing during wake and limb movements during sleep. Vigilance states included active wake (AW), quiet wake (QW), slow wave sleep I (SWSI), slow wave sleep II (SWSII), and paradoxical sleep (PS). All rats received normal saline acting as their own controls. Different rats received alpha-MSH in doses of 0.05, 0.5, 1.0, 2.0, and 6.0 microg or ACTH in doses of 0.5, 1.0, and 2.0 microg. Administered alpha-MSH caused an increase in waking behavior and prolongation of sleep latency, while ACTH stimulated waking behavior and fragmented sleep, yielding more AW and less SWSII and PS. Both hormones increased periodic movements during sleep. When administered centrally in rat, alpha-MSH and ACTH stimulate motor activity in wake, cause changes in sleep architecture, and increase periodic movements in sleep. These melanocortin hormones may play a role in the pathogenesis of RLS.
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PMID:Alpha-melanocyte stimulating hormone and adrenocorticotropic hormone: an alternative approach when thinking about restless legs syndrome? 1846 80

Opioids are an effective treatment for the signs and symptoms of Restless Legs Syndrome (RLS) and the signs and symptoms of RLS return when the opiate receptor blocker naloxone is given to opioid treated RLS patients in a blinded fashion. These data suggest that the opioid effect is specific to the opiate receptor in RLS and implicate the endogenous opioid system with its enkephalins and endorphins in the pathogenesis of RLS. We therefore measured Beta endorphin, Met-enkephalin and Leu-enkephalin levels in thalamus and substantia nigra of RLS patients (5 F - avg age 80.2 years) compared to controls (5 F, 1 M - avg age 76.3 years). One half of each brain was fixed in paraformaldehyde (PFA) in phosphate buffered saline (PBS) for pathologic evaluation and paraffin sections were stained with antibodies. Cell numbers were counted in a blinded fashion. In the thalamus, there were reductions of Beta-endorphin and Met-enkephalin positive cells by 37.5% (p=.006, effect size 2.16) and 26.4% (p=.028, effect size 1.58), respectively, in RLS patients compared to controls. There was no difference in Leu-enkephalin in the thalamus or changes in Beta endorphin, Met-enkephalin, Leu-enkephalin or Tyrosine Hydroxylase, the rate limiting step for dopamine synthesis, in the substantia nigra. Although one of the main hypotheses for pathogenesis has been that there is a dopaminergic hypofunction in RLS, this lack of decrease in Tyrosine Hydroxylase in substantia nigra is consistent with previously published post-mortem data in RLS. With Bonferroni correction, the decrease in thalamic Beta endorphin remained significant (p= .006 x 7= .042). These results suggest that there may be altered central processing of pain in RLS and these data further implicate the endogenous opioid system in the pathogenesis of RLS. The mu opiate receptor subtype may be involved in the pathogenesis of RLS as it is the target of Beta-endorphin and Met-enkephalin but not Leu-enkephalin. However, these results should be viewed as only preliminary and more advanced techniques such as stereology should be employed in future post-mortem studies. In addition, other opioid rich areas need to be explored as well as areas implicated in the pathogenesis of RLS such as the red nucleus and raphe nucleus.
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PMID:Does the endogenous opiate system play a role in the Restless Legs Syndrome? A pilot post-mortem study. 1916 16

Hypothalamic-pituitary-adrenal (HPA)-system activity is regulated by the suprachiasmatic nucleus, the primary endogenous circadian pacemaker. In addition, sleep plays an important modulatory role. However, data on HPA-system activity in sleep disorders are quite conflicting. A sensitive challenge test to assess negative feedback sensitivity of the HPA-system like the dexamethasone/corticotropin-releasing-hormone (DEX/CRH)-test has never been used so far in sleep disorders. Therefore we studied 25 obstructive sleep apnea (OSA) patients, 18 restless legs syndrome (RLS) patients, 21 patients with primary insomnia and compared them to 33 healthy controls. The dynamic response of the HPA-system was assessed by the DEX/CRH-test which combines suppression (dexamethasone) and stimulation (CRH) of the stress hormone system. After HPA-axis suppression the number of non-suppressors did not differ among groups indicating normal negative feedback sensitivity. In RLS patients ACTH levels were slightly lower compared to controls while cortisol levels were similar between groups. Following CRH stimulation we did not detect differences in ACTH- or cortisol levels and adrenocortical responsitivity to ACTH was comparable between groups. These results for the first time document normal HPA-system feedback sensitivity in various sleep disorders and suggest that abnormalities of the stress hormone system in affective disorders are unlikely due to concomitant sleep problems.
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PMID:The stress hormone system in various sleep disorders. 2150 49