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)

Although the role of serotonin (5HT) in the regulation of anterior pituitary hormone secretion is well documented, the involvement of specific 5HT receptor subtypes in this action is not yet fully elucidated. In the present work we attempted to determine the neuroendocrine role of the 5HT1A receptor subtype. This was chosen mainly because highly selective pharmacological tools are available for that subtype. 8-Hydroxy-2-(di-n-propylamino)tetralin (8OHDPAT) and ipsapirone were injected iv in conscious, freely moving male rats cannulated in the jugular vein. For the sake of comparison, a 5HT receptor agonist with preference for the 5HT1B and 5HT1C receptor subtypes 1-(m-trifluoromethyl-phenyl)piperazine (TFMPP) was also administered. Plasma PRL, ACTH, and beta-endorphin levels increased in a dose-dependent manner after 8-OHDPAT (0.01-1 mg/kg) or ipsapirone (0.5-7.5 mg/kg) injection. Maximal effects were obtained between 7-15 min. Only the highest dose of 1-(m-trifluoromethyl-phenyl)piperazine (5 mg/kg) resulted in the same response. In contrast, none of the drugs used affected plasma GH, TSH, or LH levels at any dose tested. The results indicate that 5HT1A receptors are involved in the regulation of PRL as well as ACTH and beta-endorphin secretion. 8OHDPAT was almost 40 times more potent than ipsapirone. The maximal effects of the two drugs on PRL release were comparable. In contrast, ipsapirone behaved as a partial agonist only on ACTH and beta-endorphin secretion, thus suggesting that different neuronal targets are involved in the stimulation of the three hormones by 5HT.
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PMID:Changes in anterior pituitary hormone levels after serotonin 1A receptor stimulation. 216 13

Serotonergic (5-HT) neuronal pathways regulate the release of adrenocorticotropin hormone (ACTH) from the pituitary gland probably through the action of hypothalamic corticotropin-releasing hormone (CRH). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, dose dependently (0.016-3 mg/kg s.c.) increased rat plasma ACTH concentration. This response was blocked stereoselectively by (-)-pindolol, known to have 5-HT1 antagonist properties, but not by (+)-pindolol, beta 1-, beta 2- or alpha 1-adrenoceptor, dopamine, muscarinic, 5-HT2 or 5-HT3 receptor antagonists. Similar increases of plasma ACTH were induced by other 5-HT1A receptor ligands (buspirone, ipsapirone and gepirone). These results suggest that activation of the 5-HT1A receptor induces the secretion of ACTH from the rat pituitary gland.
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PMID:Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentration. 289 20

Roxindole (5-Hydroxy-3-(4-phenyl-1,2,3,6-tetrahydropyridil-(1)-butyl)-indol) is a newly developed compound with a high dopamine autoreceptor agonistic potency at D2 receptors. Evaluation of roxindole for clinical purposes in psychiatric patients revealed that the substance has contrary to expectation merely negligible antipsychotic but considerable antidepressive effects. Interestingly it is nearly devoid of any side effects. To further characterize the endocrine effects, 1 mg roxindole was applied at 09:00 to 6 male volunteers and the effects compared to placebo. From 08:00 to 13:00 blood samples were drawn every 30 min. No effect on adrenocorticotropin and cortisol secretion was observed, neither mean plasma concentrations nor area values differed significantly. 90 min after roxindole administration an enhanced release of growth hormone could be observed, comparison of mean hormonal concentration revealed statistical significance (p < 0.05). Also the area values differed significantly (roxindole vs. placebo mean +/- SD 18.1 +/- 17.1 vs. 7.7 +/- 8.0 micrograms x h/l; p < 0.05). After roxindole also a pronounced reduction of prolactin plasma levels from 5.3 +/- 1.4 micrograms/l to 1.1 +/- 0.4 microgram/l within 150 min could be observed. Mean plasma concentrations (p < 0.05) and area values differed significantly (roxindole vs. placebo mean +/- SD 14.8 +/- 13.5 vs. 34.4 +/- 18.1; p < 0.05). Roxindole had no effect on blood pressure parameters and heart rate. The major findings of the present exploratory study are, that roxindole has potent effects on the facilitation of growth hormone secretion and the inhibition of prolactin release. Both findings are complementary and point also to interesting postsynaptic dopamine receptor agonistic effects.
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PMID:Endocrine characterization of the new dopamine autoreceptor agonist roxindole. 781 99

The pH dependence of the catalytic parameters k(cat) and K(M) has been determined for the Fe(III)Fe(II)- and Fe(III)Zn(II)-forms of bovine spleen purple acid phosphatase (BSPAP). The parameter k(cat) was found to be maximal at pH 6.3, and a pK(a) of 5.4-5.5 was obtained for the acidic limb of the k(cat) vs pH profile. Two different EPR spectra were detected for the phosphate complex of the mixed-valent diiron enzyme; their relative amounts depended on the pH, with an apparent pK(a) of 6. The EPR spectra of Fe(III)Fe(II)-BSPAP.PO(4) and Fe(III)Zn(II)-BSPAP.PO(4) at pH 5.0 are similar to those previously reported for Fe(III)Fe(II)-Uf.PO(4) and Fe(III)Zn(II)-Uf.PO(4) complexes at pH 5.0. At higher pH, a new Fe(III)Fe(II)-BSPAP.PO(4) species is formed, with apparent g-values of 1.94, 1.71, and 1.50. The EPR spectrum of Fe(III)Zn(II)-BSPAP does not show significant changes upon addition of phosphate up to 30 mM at pH 6.5, suggesting that phosphate binds only to the spectroscopically silent Zn(II). To determine whether the phosphate complexes were good structural models for the enzyme substrate complexes, these complexes were studied using rapid-freeze EPR and stopped-flow optical spectroscopy. The stopped-flow studies showed the absence of burst kinetics at pH 7.0, which indicates that substrate hydrolysis is rate limiting, rather than phosphate release. The EPR spectrum of Fe(III)Fe(II)-BSPAP.p-NPP is similar, but not identical, to that of the corresponding phosphate complex, both at pH 5 and pH 6.5. We propose that both phosphate and p-NPP bridge the two metal ions at low pH. At higher pH where the enzyme is optimally active, we propose that hydroxide competes with phosphate and p-NPP for coordination to Fe(III) and that both phosphate and p-NPP coordinate only to the divalent metal ion.
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PMID:Evidence for nonbridged coordination of p-nitrophenyl phosphate to the dinuclear Fe(III)-M(II) center in bovine spleen purple acid phosphatase during enzymatic turnover. 1043 98