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)

We describe the clinical and pathological findings in two Japanese men with small cell carcinoma of the prostate; case 1 was 58 years old and case 2 was 24 years old. Case 1 was initially diagnosed as a poorly differentiated adenocarcinoma of the prostate, stage D2, with marked elevation of serum neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and CA 19-9 levels. The patient had undergone castration and systemic chemotherapy. After three courses of chemotherapy, tumour markers were normalized. However, 6 months later serum levels of tumour markers again rose, and biopsy of the prostate revealed a small cell carcinoma component in the adenocarcinoma of the prostate and benign prostate hypertrophy. The patient was again treated with systemic chemotherapy but died within 1 year after relapse. In case 2, the patient presented with initial symptoms of lumbago and dysuria, and an enlarged prostate was radiologically diagnosed. Shortly after admission he developed ileus, and an exploratory laparotomy revealed a large tumour arising from the prostate and invading the peritoneal cavity. This tumour was pathologically diagnosed as a small cell carcinoma. The patient died shortly thereafter without responding to chemotherapy. Immunohistological evaluation was done using a panel of antibodies against NSE, chromogranin A, CEA, CA 19-9, prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), leukocyte common antigen (LCA), epithelial membrane antigen (EMA), adrenocorticotropic hormone (ACTH), calcitonin, serotonin, gastrin, vasoactive intestinal peptide (VIP), and glucagon. CEA was intensely positive in the tumour lesions from case 1, and NSE and ACTH were focally positive, and calcitonin, serotonin, CA 19-9, and PSA were weakly positive only in several cells in the tumour lesions from case 1. In the tumour lesion from case 2, NSE was intensely positive, and chromogranin A was weakly positive. These findings support the neuroendocrine nature of this neoplasm.
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PMID:Two cases of small cell carcinoma of the prostate. 900 36

Neonatal rats (3-14 days old) exhibit a period of adrenal hyporesponsiveness characterized by blunted corticosterone (B) responses to stress and reduced adrenal sensitivity to adrenocorticotropic hormone (ACTH). Several adrenomedullary peptidergic systems like vasoactive intestinal peptide (VIP) are postulated to influence cortical function. VIP is known to stimulate corticosterone secretion in vitro and to be released from the adrenal medulla following splanchnic nerve stimulation. Here, we tested whether 1) accelerated sympathetic innervation of the adrenal gland by daily L-thyroxine (T4) treatment modified the ontogeny of adrenal VIP and 2) an increase in VIP synthesis could prematurely increase adrenal sensitivity and corticosteroid output during neonatal life. Immunohistochemical VIP staining revealed a different ontogenetic pattern between adrenal regions from days 2-18 and different sensitivities to T4 treatment. Capsular staining was most abundant at all ages and increased with T4 treatment, whereas medullary staining was seen by day 18 and was not affected by T4. Throughout development, VIP receptors were detected mostly in the capsular region, but not in the adrenal cortex. Although receptor levels were not modified by T4 injections, T4 significantly enhanced VIP mRNA levels in the whole adrenal at all ages. In vivo administration of VIP (0.1-2.0 mg/kg body wt ip) to 9- to 12-day-old neonates increased pituitary ACTH, adrenal B, and aldosterone secretion significantly. Corticotropin-releasing factor immunoneutralization before VIP injection diminished VIP-induced ACTH release but still produced small but significant B and aldosterone secretion. Our results show that 1) VIP innervation of the adrenal capsule is present soon after birth and is increased by sympathetic activity whereas VIP appears only much later in the medulla and does not coincide with the onset of splanchnic innervation and 2) exogenous VIP stimulates ACTH, B, and aldosterone release during development and the effect of VIP on steroidogenic secretion is occurring through ACTH secretion, but also, at least in part, directly at the level of the adrenal gland.
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PMID:Adrenal vasoactive intestinal peptide participates in neonatal corticosteroid production in the rat. 932

Results from preclinical studies have validated the participation of neuropeptides in sleep regulation. In recent human and clinical studies it has been shown that peripheral administration of various peptides results in specific changes in the sleep electroencephalogram in humans. Furthermore, it has been demonstrated that certain peptides are common regulators of the electrophysiological and neuroendocrine components of sleep. It is now well established that the balance between the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in normal and pathological sleep regulation. In young normal subjects, GHRH stimulates slow-wave sleep and growth hormone secretion but inhibits cortisol release, whereas CRH has the opposite effect. During normal aging and during acute depression, the GHRH:CRH ratio is changed in favor of CRH, resulting in disturbances in sleep endocrine activity. In addition to GHRH, galanin, growth hormone-releasing peptide, and neuropeptide Y also promote sleep, unlike ACTH(4-9), which disturbs sleep. In elderly subjects, sleep deteriorates after acute administration of somatostatin but improves after chronic treatment with vasopressin. Vasoactive intestinal polypeptide decelerates the non-rapid eye movement-rapid eye movement cycle and advances the occurrence of the cortisol nadir. The impact of delta sleep-inducing peptide, cholecystokinin, and thyrotropin-releasing hormone on human sleep regulation is not yet clear. This paper reviews recent work investigating the influence of these various neuropeptides on sleep.
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PMID:Neuropeptides and human sleep. 945 70

We have previously reported and confirmed that vasoactive intestinal peptide (VIP) is a significant stimulator of ACTH and cortisol secretion in at least some patients with Cushing's disease. We have also found that the hormonal responses to corticotropin-releasing hormone (CRH) in VIP-responsive patients with Cushing's disease were higher than those in VIP non-responders, which suggested a linkage between the actions of CRH and VIP in this disorder. Therefore, in the present study we examined whether this linkage also exists after glucocorticoid treatment by testing the effect of dexamethasone (DEX) pretreatment (1.0 mg, intravenous bolus, 60 min before) on ACTH and cortisol responses to CRH (100 microg, i.v. bolus) and VIP (100 microg, i.v. bolus) in 7 patients with Cushing's disease who were responsive to both neuropeptides while under no DEX pretreatment. The results were that in 5 patients, DEX was able to significantly suppress the ACTH and cortisol responses to both CRH and VIP, and in the remaining 2 patients, DEX did not significantly affect the action of either CRH or VIP. This study is the first to demonstrate the parallel inhibition by DEX of ACTH and cortisol responses to CRH and VIP in Cushing's disease. Although the possibility cannot be excluded that VIP may act on CRH receptors in corticotropinomas as a partial agonist, it seems more likely that specific receptors for CRH and VIP, respectively, may concurrently express in substantial quantity in those corticotropinomas that are responsive to both neuropeptides.
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PMID:A suppressive effect of dexamethasone (DEX) on adrenocorticotropin (ACTH) response to vasoactive intestinal peptide (VIP) in Cushing's disease: a parallel modulation by DEX of ACTH responses to VIP and corticotropin-releasing hormone. 957 35

Cholecystokinin (CCK), beta-endorphin (BE), and vasoactive intestinal peptide (VIP) in peripheral blood mononuclear cells from 30 drug-naive schizophrenics compared to 22 healthy controls were studied. Patients were evaluated with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of the Negative Symptoms (SANS) at baseline (TO), and after four weeks (T4) in nine patients who were subsequently treated with haloperidol (HL). Neuropeptide concentrations in peripheral blood mononuclear cells (PBMC) were measured at TO and, for the treated patients, at T4. There was a negative correlation between CCK and SANS baseline scores and a trend for patients who responded poorly to HL (i.e. patients with a prevalence of negative symptomatology) to have lower CCK basal values.
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PMID:Cholecystokinin, beta-endorphin and vasoactive intestinal peptide in peripheral blood mononuclear cells of drug-naive schizophrenic patients treated with haloperidol compared to healthy controls. 957 1

There is extensive evidence that serotonin (5-HT) is implicated in the neuroendocrine control regulating the secretion of several anterior pituitary hormones. It has also been reported that the posterior pituitary is necessary for prolactin (PRL) response to 5-HT as well as to suckling, in which 5-HT implication has been demonstrated. As we have previously shown that vasoactive intestinal peptide (VIP) mediates through an autocrine or paracrine action the PRL release induced by insulin-like growth factor I, thyrotropin-releasing hormone (TRH) and dopamine withdrawal, the aim of the present work was to determine whether 5-HT has a direct action on pituitary secretion and to study the possible role of pituitary VIP in this situation. Cells from the anterior pituitary lobe (AP) were cultured either alone or together with cells from the posterior pituitary lobe (PP). As melanotropes from PP express glucocorticoid receptors in vitro, both AP cultures and cocultures of AP/PP cells were incubated in the presence or absence of corticosterone (0.1 microg/ml), thus designing four experimental conditions. Then both AP and mixed cultures were incubated with 5-HT (100 nM) for 20, 45 and 180. The release of PRL, growth hormone (GH), corticotropin (ACTH) and luteinizing hormone (LH) was stimulated by 5-HT, but only in cocultures of AP/PP cells preincubated with corticosterone, whereas follicle-stimulating hormone and thyroid-stimulating hormone release was not modified. As AP cultures did not show any response to 5-HT, both in the presence or absence of corticosterone, and as melanotropes are the main cellular type present in the PP cultures, we studied the response of alpha-melanocyte-stimulating hormone (alphaMSH) to 5-HT in PP cells cultured with or without corticosterone. Serotonin did not modify alphaMSH release either in the absence or the presence of corticosterone. VIP release was also stimulated by 5-HT in the cocultures, and the time response profile was only similar to that of PRL. In order to study whether pituitary VIP is implicated in 5-HT action, cocultures preincubated with corticosterone were incubated in the presence of 5-HT, a VIP-receptor antagonist (VIP-At) or simultaneously with 5-HT plus VIP-At. PRL response to 5-HT was abolished by the simultaneous presence of VIP-At, whereas GH, ACTH and LH response remained unchanged. These data demostrate that: (1) 5-HT stimulates the secretion of PRL, GH, ACTH, LH and VIP acting directly at pituitary level on PP, probably by releasing an unidentified mediator from melanotropes; (2) glucocorticoids make the response of AP cells to 5-HT possible due to the presence of PP cells in the coculture; (3) PRL response to 5-HT is mediated through an autocrine and/or paracrine action of VIP.
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PMID:Direct action of serotonin on prolactin, growth hormone, corticotropin and luteinizing hormone release in cocultures of anterior and posterior pituitary lobes: autocrine and/or paracrine action of vasoactive intestinal peptide. 982

Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) caused a dose-dependent increase in met-enkephalin secretion and increased production of met-enkephalin peptide and proenkephalin A (PEnk) mRNA in bovine chromaffin cells, at concentrations as low as 300 pM. PACAP-38 was less potent than PACAP-27, but had similar effects. Vasoactive intestinal polypeptide (VIP) (1-100 nM) was without appreciable effect on either enkephalin secretion or biosynthesis, implicating PACAP type I receptors in PACAP-stimulated enkephalin secretion and synthesis. PACAP type I receptors can activate adenylate cyclase and stimulate phospholipase C through heterotrimeric G protein interactions, leading to increased intracellular cyclic AMP (cAMP), inositol triphosphate (IP3)-mediated calcium mobilization, and calcium- and diacylglycerol (DAG)-mediated protein kinase C (PKC) activation. Enkephalin secretion evoked by 10-100 nM PACAP-27 was not inhibited by 1 microM (-)-202-791, an L-type specific dihydropyridine calcium channel blocker, but was inhibited 65-80% by the arylalkylamine calcium channel blocker D600. Forty mM potassium-evoked secretion was inhibited > 90% by both D600 and (-)-202-791, 25 microM forskolin-induced secretion was blocked < 50% by D600 and was unaffected by (-)-202-791, and 100 nM phorbol myristate acetate (PMA)-induced secretion was unaffected by either D600 or (-)-202-791. Enkephalin biosynthesis was increased by 10 nM PACAP-27, as measured by increased met-enkephalin pentapeptide content and PEnk A mRNA levels. PACAP-, forskolin-, and PMA-stimulated enkephalin synthesis were not blocked by D600 or (-)-202-791. Elevated potassium-induced enkephalin biosynthesis upregulation was completely blocked by either D600 or (-)-202-791 at the same concentrations. PACAP acting through type I PACAP receptors couples calcium influx-dependent enkephalin secretion and calcium influx-independent enkephalin biosynthesis in chromaffin cells. Restriction of the effects of enhanced calcium influx to stimulation of secretion, but not of biosynthesis, is unique to PACAP. By contrast, potassium-induced enkephalin biosynthesis upregulation is completely calcium influx dependent, specifically via calcium influx through L-type calcium channels. We propose that subpopulations of voltage-dependent calcium channels are differentially linked to intracellular signal transduction pathways that control neuropeptide gene expression and secretion in chromaffin cells.
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PMID:PACAP activates calcium influx-dependent and -independent pathways to couple met-enkephalin secretion and biosynthesis in chromaffin cells. 982 85

Since the time of Freud, psychiatry has embraced the proposition that physiological and/or psychological stress precipitates various psychiatric disorders. To this effect, we propose that a continuum of liability obtains between stress, anxiety states and anorexia nervosa--a continuum which is grounded on a cytokine profile common to each of these conditions. For example, the biological response to stress, anxiety states and anorexia nervosa includes the elevation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and downregulation of interferon-gamma (IFN-gamma). Sustained elevation of IL-1 beta and TNF-alpha dysregulates both somatostatin and insulin secretion, the latter of which influences regional cerebral blood flow (rCBF) and brain energy metabolism. In addition, IL-1 beta and TNF-alpha influence the expression of certain crucial neuropeptides, which are known to be associated with anxiety states and anorexia nervosa. These neuropeptides include: beta-endorphin, cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). beta-endorphin effects glucose metabolism in the limbic system, CCK increases the release of beta-endorphin from the anterior pituitary, NPY is a powerful anxiolytic that regulates beta-endorphin and insulin, while VIP indirectly regulates the expression of TNF-alpha through the inhibition of interleukin-4 (IL-4).
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PMID:Tumor necrosis factor-alpha: is there a continuum of liability between stress, anxiety states and anorexia nervosa? 1034 Feb 96

Pituitary adenylate cyclase-activating polypeptide (PACAP), the new hypophysiotropic factor member of the vasoactive intestinal peptide (VIP)/secretin/glucagon/GHRH family of neuropeptides, exerts its biological action by interacting with both PACAP-selective type I receptors (PAC1) and type II receptors (VPAC1), which bind both PACAP and VIP. The placenta is a site of production of hypophysiotropic factors that participate in the control of local hormone production, as well as the respective hypothalamic-pituitary neurohormones. In the present study, we show the expression of PACAP gene and irPACAP distribution within rat and human placental tissues, by means of RT-PCR and immunohystochemical experiments. In both rat and human placenta, we evaluated the expression of PAC1 gene by Northern hybridization analysis performed with a 32P-labeled 706 nt complementary DNA probe, derived from the full-length coding region of the rPAC1 complementary DNA. The results of these experiments demonstrate the presence, in both human and rat placenta, of a 7.5-kb transcript similar in size to those detected in the ovary, brain, and hypothalamus. Alternative splicing of two exons occurs in human and rat PAC1 gene generating splice variants with variable tissue-specific expression. To ascertain which of the splice variants were expressed in placental tissue we performed RT-nested PCR using primers flanking the insertion sequence termed hip/hop cassette in rat or SV1/SV2 box in human gene. Electrophoretic analysis of the PCR products showed a different pattern of expression of messenger RNA splicing variants in human and rat placenta. In particular, the rat placenta expresses the short PAC1 receptor (PAC1short), the rPAC1-hip or hop (which are indistinguishable with the primers used), and the rPAC1-hip-hop, whereas the human placenta expresses only the PAC1SV1 (or SV2) variant, structurally homologous to the rat PAC1 hip (or hop). Sequence analysis of the human PCR-amplified PAC1 variant was therefore carried out and revealed that human placenta only expresses the PAC1SV2 isoform. The presence and characterization of PACAP binding sites was then investigated in human placenta by radioligand binding studies performed on crude membrane preparation using [125I]PACAP27 as tracer. Scatchard analysis of the binding results revealed the presence of two binding sites, one with high affinity and low capacity (Kd 0.33+/-0.04 nM; Bmax 36.9+/-12.1 fmol/mg protein) and one with low affinity and high capacity (Kd 24+/-6.9 nM, Bmax 9.3+/-0.19 pmol/mg protein). The relative potencies of PACAP-related peptides for inhibition ofradioligand binding were: PACAP27 > or = PACAP38 > VIP, whereas GHRH and other unrelated peptides, such as CRH and beta-endorphin, did not inhibit [125I]PACAP27 binding. In conclusion, in this study, we provide evidence for the expression of PACAP within rat and human placenta. We also demonstrate that both human and rat placenta express the PAC1 gene and that the human tissue has binding sites for PACAP. These findings may suggest a role for PACAP in the regulation of placental physiology through autocrine and/or paracrine mechanisms.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta. 1069 93

The prolactin (PRL)-releasing activity (PRA) in the bovine hypothalamic extract (BHE) was compared to that of known substances with PRA and further characterized by gel filtration and reversed-phase high performance liquid chromatography (RP-HPLC). Crude BHE produced marked dose-dependent stimulation of PRL secretion from the cultured rat adenohypophysial cells. Among the synthetic substances examined, vasoactive intestinal peptide (VIP), thyrotropin-releasing hormone (TRH) and beta-endorphin (END) showed significant PRA. However, the flatter dose-response slope for TRH compared with BHE or the small amounts of VIP and END in BHE suggested that these peptides could not account for the major active elements of BHE. Oxytocin and interleukin-1beta were also tested, but they exhibited no PRA in our assay system. Gel filtration of BHE on the Sephadex G-100 column yielded two peaks of PRA distinct from TRH, VIP and END. One eluted in the void and the other in more retarded fractions. The latter fractions were pooled and subjected to the two-step RP-HPLC. The PRA was separated into three peaks designated peaks I, II and III in the first RP-HPLC experiment. Furthermore, the second RP-HPLCs with finer resolution revealed that peak II as well as peak III consisted of three peaks, while peak I eluted as a single peak. Most of these seven PRA peaks exhibited different RP-HPLC profiles from those of the newly characterized PRL-releasing peptides. These findings again provide confirmatory evidence that BHE contained unique factors different from the above known substances.
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PMID:Multiple prolactin-releasing activity in the bovine hypothalamic extract. 1072 8


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