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)

Previous work has shown corticotropin-releasing hormone (CRH) stimulation of beta-endorphin (END) secretion from hypothalamus. We tested the hypothesis that CRH stimulation of beta-END (measured by radioimmunoassay) from hypothalamic explants is dependent on: (1) ovine CRH dose, (2) pattern and sequence of CRH stimulation, (3) androgen status, and (4) hypothalamic age. Hypothalami from adult male rats and day 17 fetal rats were studied. In adult hypothalami, CRH-stimulated immunoreactive (IR)-beta-END secretion with 10(-7) M was greater than that with 10(-8) M CRH and showed dose-dependent stimulation. Serial stimulation for 20 min by 10(-8) M CRH followed by a 40 min interval without CRH stimulation resulted in a brief stimulation of secretion of IR-beta-END and also secretion of IR-alpha-melanocyte-stimulating hormone (MSH), another peptide derived from pro-opiomelanocortin, the precursor of beta-END. Subsequent stimulation with 10(-6) M CRH showed a desensitization to stimulation despite readily releasable pools of IR-beta-END shown by potassium-induced depolarization. In addition, prolonged stimulation for 1 h with 10(-7) M CRH or increasing concentrations of CRH produced a sustained increase in IR-beta-END release as long as CRH was present. Dihydrotestosterone treatment had no effect on basal nor CRH-stimulated IR-beta-END release in orchiectomized rats. The pattern of IR-beta-END secretion from fetal hypothalamic explants exposed briefly (20 min) or for a prolonged period (1 h) to CRH was similar to that from adult explants. These results demonstrate that: (1) CRH-stimulated IR-beta-END secretion from hypothalamus is dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:In vitro regulation of immunoreactive beta-endorphin secretion from adult and fetal hypothalamus by sequential stimulation with corticotropin-releasing hormone. 132 6

Midbrain raphe serotonin (5-HT) neurons can influence the pituitary-adrenal axis. The midbrain raphe nuclei also contain a number of non-5-HT neurons, including gamma-aminobutyric acid (GABA) interneurons which can modulate 5-HT neuronal activity. We investigated the effects of intraraphe injections of the GABAA agonist, muscimol, on serum adrenocorticotropin hormone (ACTH) and corticosterone concentrations. Rats were infused with muscimol (0, 25, 50, and 100 ng in 0.5 microliters saline) into the median raphe nucleus (MR). The animals were killed 30 min later, and trunk blood was collected for measurement of serum concentrations of ACTH and corticosterone by radioimmunoassay. Muscimol dose dependently increased plasma concentrations of these two pituitary-adrenal hormones. In order to determine the role of MR 5-HT neurons in these effects, separate groups of implanted animals were infused with either the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) or ascorbic acid vehicle into the MR. Two weeks later, the animals were infused with muscimol (100 ng in 0.5 microliters) and sacrificed as above. Treatment with 5,7-DHT, which markedly reduced hippocampal concentrations of 5-HT (-83%) and 5-HIAA (-73%), did not block intra-MR muscimol-induced elevations in ACTH and corticosterone. Thus, 5-HT neurons within the MR apparently do not mediate the increased activity of the pituitary-adrenal axis produced by stimulation of MR GABAA receptors.
 ...
PMID:Muscimol injections into the median raphe nucleus increase serum ACTH and corticosterone concentrations via a nonserotonergic mechanism. 172

Serotonin depleters, 5,7-dihydroxytryptamine (5,7-DHT) and p-chlorophenylalanine (PCPA), were injected into adult male rats and beta-endorphin (beta-EP), alpha-melanotropin (alpha-MSH) and adrenocorticotropin (ACTH) levels in rat brain and pituitary were each estimated by radioimmunoassay combined with a gel column chromatography. (1) 5,7-DHT, injected intracerebroventricularly combined with pargyline, decreased the levels of immunoreactive-beta-EP, -alpha-MSH and -ACTH significantly and concomitantly in hypothalamus, thalamus, and brainstem. (2) PCPA, repeatedly injected intraperitoneally 8 times every 3 days, decreased the levels of these peptides in some of these brain regions. (3) There was no significant change of IR-beta-EP, -alpha-MSH, -ACTH in the anterior and the intermediate-posterior pituitaries after the treatment of 5,7-DHT or PCPA. (4) A single injection of the same dose of PCPA induced no significant effects on these peptide levels in both brain and pituitary. These data suggest that central serotoninergic neurons might affect beta-EP-alpha-MSH-ACTH containing neurons in rat brain.
 ...
PMID:Effects of serotonin depleters on the contents of beta-endorphin, alpha-melanotropin and adrenocorticotropin in rat brain and pituitary. 609 4

This study tested the effect of brain serotonin (5-HT) depletion on the secretion of oxytocin (OT), vasopressin (VP), and adrenocorticotropin (ACTH) due to an osmotic load. The 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) was used to deplete brain 5-HT. The OT, VP, and ACTH osmotic sensitivity (slope of delta[OT]/delta[Osm]) and the osmotic threshold (X intercept of delta[OT]/delta[Osm]) were evaluated. Depletion of brain 5-HT decreased the OT osmotic sensitivity by > 80% (p < 0.001) without changing the OT osmotic threshold. Brain 5-HT depletion had no effect on the VP osmotic sensitivity and increased the VP osmotic threshold from 287.8 +/- 1.5 to 293.1 +/- 2.0 mOsm/kg (p < 0.05). The plasma ACTH increase due to infusion of hypertonic saline was not affected by brain 5-HT depletion. Brain 5-HT depletion significantly (p < 0.01) decreased the pituitary content of OT and VP by 38 and 32%, respectively, without changing ACTH content. These results provide evidence for a functional role of serotonergic neurons in osmoregulation of plasma and pituitary concentration of OT and VP, but not ACTH.
 ...
PMID:The role of serotonergic neurons in intravenous hypertonic saline-induced secretion of vasopressin, oxytocin, and ACTH. 822 Nov 54

In the present study, we examined denervation-induced changes in the sensitivity of hypothalamic postsynaptic serotonin1A (5-HT1A) receptor function with respect to changes in the dose-dependent elevation in plasma hormones [adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin, prolactin, renin and vasopressin] by the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT). Rats received intracerebroventricular (i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (0.1% ascorbate in saline) 3 weeks before challenge with increasing doses of 8-OH-DPAT (0, 10, 50 or 200 micrograms/kg s.c.). The effectiveness of 5,7-DHT-induced destruction of serotonergic neurons was confirmed by a 93% reduction in [3H]paroxetine-labeled 5-HT uptake sites in the hypothalamus. No changes in basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and vasopressin were observed in rats that received i.c.v. 5,7-DHT injections. The dose-response curves for 8-OH-DPAT-induced elevations of plasma corticosterone and prolactin levels were shifted to the left in rats treated with 5,7-DHT, whereas no significant difference in the ACTH dose-response curve was observed between rats treated with vehicle and rats treated with 5,7-DHT. In contrast, the maximal oxytocin response to 8-OH-DPAT was attenuated in rats treated with 5,7-DHT. A 5,7-DHT-induced decline in the synthesis of oxytocin could explain this phenomenon. Although 8-OH-DPAT did not increase plasma levels of renin or vasopressin in rats treated with vehicle, 8-OH-DPAT produced an elevation (75%) in plasma renin concentration but not in vasopressin levels in rats that received i.c.v. injections of 5,7-DHT. No change was observed in [3H]8-OH-DPAT labeled 5-HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic serotonergic nerve terminals produces supersensitivity of some neuroendocrine responses to 8-OH-DPAT independent of changes in the density of hypothalamic 5-HT1A receptors.
 ...
PMID:Alterations in 8-hydroxy-2-(dipropylamino)tetralin-induced neuroendocrine responses after 5,7-dihydroxytryptamine-induced denervation of serotonergic neurons. 965 67

Although the involvement of both endogenous opioid and serotonergic systems in modulation of pain and emotion was suggested, the neurochemical interaction between these systems in the brain has not previously been studied directly. Herein, the effects of the local application of serotonin (5-HT) and fluoxetine (a 5-HT reuptake inhibitor) on extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens were assessed in freely moving rats using in vivo microdialysis. The mean basal concentrations of beta-endorphin in dialysates obtained from the arcuate nucleus and nucleus accumbens were 259.9 and 143.3 pM, respectively. Specific lesion of the serotonergic system by 5,7-dihydroxytryptamine (5,7-DHT) caused a significant decrease in these dialysate beta-endorphin levels. When 5-HT (0.25-5 microM) was added to the perfusion solution, the levels of beta-endorphin in the dialysate from the arcuate nucleus increased (186-296% of baseline), in a concentration-dependent manner. In the nucleus accumbens, 0.5 and 2 microM 5-HT in the perfusion fluid did not affect the levels of beta-endorphin in the dialysate, whereas 5 and 10 microM 5-HT caused an increase of approximately 190% of baseline. When fluoxetine (250 microM) was present in the perfusing solution, the levels of beta-endorphin in the dialysates from the arcuate nucleus and nucleus accumbens increased two- to threefold. This effect was not obtained in the 5,7-DHT-lesioned rats. Thus, 5-HT, either endogenously or exogenously delivered, appears to facilitate the release of beta-endorphin in the arcuate nucleus and nucleus accumbens. This indication of an interaction between serotonergic and endorphinic systems may be relevant for assessing pain and mood disorder circuits and the mode of action of antidepressant drugs.
 ...
PMID:Serotonin-mediated increases in the extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens: a microdialysis study. 1058 20