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)

An imbalance between serotonin-2A (5-HT2A) and 5-HT1A receptors may underlie several mood disorders. The present studies determined whether 5-HT2A receptors interact with 5-HT1A receptors in the rat hypothalamic paraventricular nucleus (PVN). The sensitivity of the hypothalamic 5-HT1A receptors was measured as oxytocin and adrenocorticotropic hormone (ACTH) responses to the 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide [(+)8-OH-DPAT] (40 microg/kg s.c.). The 5-HT(2A/2C) receptor agonist (-)DOI [(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl] (1 mg/kg s.c.) injected 2 h prior to (+)8-OH-DPAT significantly reduced the oxytocin and ACTH responses to (+)8-OH-DPAT, producing a heterologous desensitization of the 5-HT1A receptors. Microinjection of the 5-HT2A receptor antagonist MDL100,907 [(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol; 0, 10, or 20 nmol, 15 min prior to (-)DOI] into the PVN dose-dependently prevented the desensitization of 5-HT1A receptors induced by the 5-HT2A receptor agonist (-)DOI. Double-label immunocytochemistry revealed a high degree of colocalization of 5-HT1A and 5-HT2A receptors in the oxytocin and corticotropin-releasing factor neurons of the PVN. Thus, activation of 5-HT2A receptors in the PVN may directly induce a heterologous desensitization of 5-HT1A receptors within individual neuroendocrine cells. These findings may provide insight into the long-term adaptation of 5-HT1A receptor signaling after changes in function of 5-HT2A receptors; for example, during pharmacotherapy of mood disorders.
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PMID:Desensitization of 5-HT1A receptors by 5-HT2A receptors in neuroendocrine neurons in vivo. 1506 30

Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is characterized by nitric oxide deficiency. Tetrahydrobiopterin (BH4) is an essential cofactor for the enzyme nitric oxide synthase and glucocorticoids have been reported to reduce cytokine-induced BH4 production. Accordingly we hypothesized that ACTH-induced hypertension would be reversed by BH4 supplementation. Male Sprague-Dawley rats (n = 33) were treated with BH4 in vehicle (10 mg/kg/day i.p.) or vehicle alone (5 mg/kg/day i.p. of ascorbic acid in 4 mM HCl) for 10 days. ACTH (0.2 mg/kg s.c.) or saline daily injection was started 2 days after BH4 or vehicle treatment and continued for 8 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. Treatment with HCl, ascorbic acid or BH4 alone had no effect on SBP. In saline treated rats, neither BH4 nor its vehicle modified SBP. In ACTH treated rats, SBP was increased in both BH4 (from 128 +/- 6 to 142 +/- 4 mmHg, T0 to T10, P < 0.0005, one way ANOVA) and vehicle groups (from 127 +/- 3 to 158 +/- 7 mmHg, T0 to T10, P < 0.001, one way ANOVA). There was no significant difference in SBP between BH4 + ACTH treated and vehicle + ACTH treated rats. Thus, daily injection of BH4 (10 mg/kg i.p.) failed to prevent the development of ACTH-induced hypertension in rat.
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PMID:Role of tetrahydrobiopterin in adrenocorticotropic hormone-induced hypertension in the rat. 1513 1

We previously demonstrated colocalization of serotonin 1A (5-HT(1A)) and serotonin 2A (5-HT(2A)) receptors in oxytocin and corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus (PVN). Because a functional imbalance between hypothalamic 5-HT(1A) and 5-HT(2A) receptors has been implicated in several neuropsychiatric disorders, in this study we investigated whether acute in vivo activation of 5-HT(1A) receptors in the PVN results in desensitization of 5-HT(2A) receptor signaling. Functional desensitization of hypothalamic 5-HT(2A) receptors was assessed via a reduction in oxytocin and adrenocorticotropin (ACTH) responses to the 5-HT(2A/2C) receptor agonist (-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl [(-)DOI]. We report here that a single systemic injection of the 5-HT(1A) receptor agonist (+)-8-hydroxy-2-(di-n-propylamino)-tetralin [(+)8-OH-DPAT] (200 microg/kg) significantly reduced the 5-HT(2A) receptor-mediated oxytocin responses for at least 72 h. Direct intraparaventricular injection of (+)8-OH-DPAT (0.2 nmol) 24 h before a submaximal dose of (-)DOI (0.35 mg/kg) significantly inhibited the 5-HT(2A) receptor-mediated increases in both oxytocin and ACTH (-39 and -16%, respectively). In addition, the (+)8-OH-DPAT-induced desensitization of the 5-HT(2A) receptor-mediated oxytocin but not the ACTH response was inhibited in rats pretreated with either a systemic (0.1 mg/kg) or intraparaventricular (10 nmol) injection of the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635). This is the first in vivo demonstration of a prolonged heterologous intracellular desensitization of 5-HT(2A) receptors after acute activation of 5-HT(1A) receptors. These findings may provide insight into the long-term heterologous interactions between 5-HT(1A) and 5-HT(2A) receptor signaling that could occur in response to antidepressants, antipsychotics, or drugs of abuse that target these receptor subtypes.
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PMID:Single exposure to a serotonin 1A receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin, produces a prolonged heterologous desensitization of serotonin 2A receptors in neuroendocrine neurons in vivo. 1715 60

Studies in both rodents and humans have shown that acute inflammatory pain experienced during the perinatal period produces long-term decreases in pain sensitivity (hypoalgesia) (Grunau et al., 1994a, 2001; Ren et al., 2004; LaPrairie and Murphy, 2007). To date, the mechanisms underlying these long-term adaptations, however, have yet to be elucidated. The present studies tested the hypothesis that neonatal inflammatory pain induces an upregulation in endogenous opioid tone that is maintained into adulthood, and that this increase in opioid tone provides the underlying mechanism for the observed hypoalgesia. On the day of birth (P0), inflammatory pain was induced in male and female Sprague-Dawley rats by intraplantar administration of carrageenan (CGN; 1%). In adulthood (P60), these animals displayed significantly increased paw withdrawal latencies in response to a noxious thermal stimulus in comparison to controls. Systemic administration of the brain-penetrant opioid receptor antagonist naloxone HCl, but not the peripherally restricted naloxone methiodide, significantly attenuated the injury-induced hypoalgesia. Direct administration of naloxone HCl or antagonists directed at the mu or delta opioid receptors into the midbrain periaqueductal gray (PAG) also significantly reversed the injury-induced hypoalgesia in adult rats. Parallel anatomical studies revealed that inflammatory pain experienced on the day of birth significantly increased beta-endorphin and met/leu-enkephalin protein levels and decreased opioid receptor expression in the PAG of the adult rat. Thus, early noxious insult produces long-lasting alterations in endogenous opioid tone, thereby profoundly impacting nociceptive responsiveness in adulthood.
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PMID:Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal gray. 1986 48


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