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)

Phencyclidine (PCP) has been found to affect neuroendocrine function by altering the release of the anterior pituitary hormones, adrenocorticotrophin, luteinizing hormone and prolactin. The purpose of this study was to examine the effect of PCP on release of the two pituitary hormones also derived from the adrenocorticotropin precursor, namely, alpha-melanocyte-stimulating hormone and beta-endorphin (beta-E), synthesized in the neurointermediate and anterior lobes of the pituitary. At behaviorally active doses, PCP administered i.c.v. increased plasma levels of immunoreactive beta-E (i beta-E) without affecting the concentration of immunoreactive alpha-melanocyte-stimulating hormone, suggesting that PCP increased the release of beta-E from only the anterior lobe of the pituitary. Dexamethasone pretreatment blocked the PCP-induced increase in i beta-E which indicated further the anterior lobe effects of PCP. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate), a selective PCP ligand, at behaviorally active doses also increased the plasma concentration of i beta-E. The dose-response curves for induction of behavior was very different from that for increasing the concentration of i beta-E in plasma. The increase in release of i beta-E was stereoselective as (+)-(1-(1-phenylcyclohexyl)-3 methylpiperidine but not (-)-(1-(1-phenylcyclohexyl)-3 methylpiperidine increased release of i beta-E. The increase in plasma levels of beta-E was not due to an interaction with opioid receptors because naloxone did not block PCP-induced release of beta-E. In vitro, PCP also significantly increased release of i beta-E from anterior lobe of the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phencyclidine increased release of beta-endorphin from anterior lobe of the pituitary. 165 42

The release of free [3H]arachidonic acid and its metabolites (AAM) from mouse embryo cortical neurones cultured in serum-free medium stimulated by beta-endorphin C-terminal dipeptide (glycl-L-glutamine, Gly-Gln) was investigated. Gly-Gln but not the related dipeptide, glycyl-glutamic acid, caused a 2-fold elevation of AAM release which was blocked in the absence of extracellular calcium, in the presence of 5 mM magnesium and by the phospholipase A2 (PLA2) inhibitor, mepacrine. Other proopiomelanocortin (POMC) peptides did not elicit AAM release. The response to Gly-Gln was unaffected by D-amino-2-phospho-5-valeric acid (AP5) and 7-chlorokynurenic acid (7-ClKY), antagonists respectively at the ligand and allosteric glycine binding sites of the NMDA glutamate receptor subtype. However, it was inhibited in a dose-dependent manner by antagonists at the phencyclidine (PCP) and sigma sites. The results suggest that Gly-Gln causes AAM release by activating PLA2 through the mediation of a PCP/sigma-like receptor.
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PMID:Beta-endorphin C-terminal peptide evokes arachidonic acid release from cortical neurones. 190 34

Phencyclidine (PCP) markedly stimulates the pituitary-adrenal axis in the rat, inducing the release of adrenocorticotropin (ACTH) and corticosterone. However, the site or sites where PCP produces these effects is not known. This study sequentially examined the effects of PCP on the different components of the central nervous system-pituitary-adrenal axis. PCP did not produce corticosterone release in dispersed adrenal cells in vitro, nor did it stimulate the release of corticosterone in hypophysectomized rats, showing that PCP-induced corticosterone release in intact animals is secondary to the release of ACTH from the pituitary. PCP failed to alter either the basal or the corticotropin releasing factor-induced release of ACTH from superfused pituitaries in vitro, indicating that PCP does not act directly at the level of the pituitary. PCP increased plasma levels of ACTH in adrenalectomized rats, demonstrating that PCP does not stimulate the release of ACTH only by blocking glucocorticoid negative feedback mechanisms. PCP stimulated the release of both ACTH and corticosterone when given by injection directly into brain via the lateral cerebral ventricles. These results indicate that PCP activates the pituitary-adrenal axis by acting at a site or sites within the central nervous system, leading to the subsequent release of ACTH from the pituitary.
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PMID:Determination of the loci of action of phencyclidine on the CNS-pituitary-adrenal axis. 216 1

A variety of imaging procedures were performed in 28 patients with ectopic adrenocorticotropic hormone (ACTH) syndrome in an attempt to localize the ACTH-producing tumor. Diagnosis was made on the basis of removal of an ACTH-producing tumor or biopsy of metastases in the 19 patients with a proved source and the absence of ACTH gradients in bilateral samples of the inferior petrosal sinuses in the nine patients in whom an ACTH-secreting tumor had not been localized. Eleven bronchial carcinoids, two thymic carcinoids, three pheochromocytomas, and three islet-cell tumors constituted the proved sources. The condition has been cured in eight patients, six are alive with residual tumor, and five have died. Of the nine patients with undetected sites of ACTH production, one has died of pneumocystis pneumonia and eight are being treated medically or with bilateral adrenalectomy. Computed tomography (CT) of the chest and abdomen was the most helpful study in the detection of these tumors. Selective arteriography (bronchial and visceral), systemic and portal venous sampling, and iodine-131 meta-iodobenzylguanidine scintigraphy failed to demonstrate tumors when findings at CT were negative. Bronchial carcinoids constituted most of the ACTH-secreting tumors in this study (58%) and in a review of four large series (47%). To assure early detection of these potentially malignant tumors, pulmonary CT should be performed every 6 months, even after hypercortisolism has been medically or surgically controlled.
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PMID:Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients. 254 19

Phencyclidine (PCP) is a widely used drug of abuse; however, little is known of its effects on neuroendocrine function. The present study characterized the effects of the acute and chronic administration of PCP on the release of adrenocorticotropin, corticosterone and prolactin in the rat. For the acute studies, PCP hydrochloride (0.5-10.0 mg/kg s.c.) was administered and the subjects were sacrificed 15 to 300 min later. The acute administration of PCP produced rapid and long-lasting increases in plasma levels of adrenocorticotropin and corticosterone but decreased plasma levels of prolactin. For the chronic studies, PCP (1.0-20.0 mg/kg/day s.c.) was injected daily and the subjects sacrificed 60 min after injection on day 15. PCP continued to stimulate the pituitary-adrenal axis after chronic administration; however, there was a decrease in the magnitude of response, indicating the development of some degree of tolerance. In contrast, none of the doses of PCP tested decreased plasma prolactin levels in chronically treated subjects. There were no differences in plasma or brain levels of PCP in the chronically PCP-treated rats, indicating that tolerance was not due to changes in the biodisposition of PCP. These results indicate that PCP disrupts neuroendocrine function markedly in the rat. The differential development of tolerance to the effects of PCP on the pituitary-adrenal axis and prolactin release may indicate that different neurochemical substrates underlie the effects of PCP on different endocrine systems.
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PMID:Characterization of the effects of the acute and chronic administration of phencyclidine on the release of adrenocorticotropin, corticosterone and prolactin in the rat: evidence for the differential development of tolerance. 254 36

Cytomegalovirus pneumonia, Pneumocystis carinii pneumonia, and pulmonary and disseminated aspergillosis occurred simultaneously in a 66-year-old white man with oat cell carcinoma and ectopic corticotropin production. Hypokalemia, a recent normal chest roentgenogram, and a large left adrenal mass on a computed tomographic scan confused the initial clinical evaluation. The aspergillosis proved fulminant and lethal.
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PMID:Three opportunistic infections associated with ectopic corticotropin syndrome. 255 32

The potent opiate radioligands [3H]etorphine, [3H]ethylketocyclazocine (EKC), and [3H]naloxone, bound specifically and saturably to a single class of membrane-binding sites in rat neurointermediate lobe (NIL), with Kd values of 3.7, 24, and 51 nM, respectively. In the hypothalamus (Ht), [3H]etorphine bound to specific and saturable sites with a Kd of 2.9 nM. Binding-inhibition studies with [3H]etorphine and unlabeled etorphine-HCl as well as [3H]EKC and unlabeled EKC, revealed high and low affinity binding sites in rat Ht and NIL as well as in the neural lobe of the bovine pituitary gland. [3H]naloxone also bound specifically to two classes of sites in Ht membranes, but to only a single class of low affinity sites in NIL membranes. Specific binding represented 80-90% of total [3H]etorphine binding, about 75% of total [3H]EKC binding, and 45-55% of total [3H]naloxone binding at 22 C in NIL and Ht, respectively. Relative binding potencies derived from Ki values for binding-inhibition studies of [3H]etorphine with opioid peptides and opiates were: NIL, etorphine-HCl greater than dynorphin A greater than naloxone-HCl greater than dynorphin-(1-9) greater than beta-endorphin much greater than alpha-neoendorphin approximately (Leu5)enkephalin approximately DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-ol); Ht, etorphine HCl greater than naloxone-HCl greater than beta-endorphin greater than dynorphin A much greater than DAGO greater than morphiceptin much greater than (Leu5)enkephalin. Specific [3H]etorphine binding was also demonstrable after preincubation of NIL membranes with DAGO and (Leu5)enkephalin and after preincubation of Ht membranes with morphiceptin and (Leu5)enkephalin; such binding could be displaced by nonradioactive dynorphin A. In addition, [3H]etorphine binding to bovine neural lobe was displaceable by naloxone-HCl, with an ED50 of 43 nM. Specific ligands for sigma-opiate receptors, such as (+)SKF 10,047 (N-allylnorcyclazocine), phencyclidine (PCP), and (-)cyclazocine, displaced specifically bound [3H]etorphine and [3H]EKC from NIL membranes only at high (micromolar) concentrations. However, specific [3H]PCP sites were of higher affinity in NIL and Ht membranes, with similar Kd values of 102 and 190 nM respectively, and different concentrations (0.15 and 1.32 pmol/mg protein, respectively). These data have revealed several differences in the opiate-binding properties of rat Ht and NIL membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Opiate receptor subtypes in the rat hypothalamus and neurointermediate lobe. 303 71

The study investigated the interaction between phencyclidine (PCP) and morphine in affecting the levels of met-enkephalin, dopamine, DOPAC and HVA in mice. Morphine 5 mg/kg alone and PCP 10 mg/kg alone failed to change the levels of met-enkephalin in the midbrain and striatum. However, PCP in combination with morphine produced an increase in met-enkephalin levels and a decrease in HVA levels. In the midbrain, there was a direct relationship between the decrease in met-enkephalin levels and the increase in HVA levels. These results suggest that PCP may change the function in dopaminergic and enkephalinergic neuronal systems in the midbrain and/or striatum.
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PMID:Effects of phencyclidine in combination with morphine on the levels of met-enkephalin, dopamine, DOPAC and HVA in discrete brain areas of mice. 383 60

Evidence from a variety of experimental models has suggested the existence of mu 1, mu 2 and delta binding sites for morphine and the enkephalins in the central nervous system. Additional biochemical experiments now support this concept of a common high affinity site for opiates and opioid peptides. Mu sites have now been implicated in a number of pharmacological actions, including supraspinal analgesia, prolactin release, and catalepsy, but not in others (spinal analgesia, respiratory depression, and the guinea pig ileum). The hypothesis of mu 1 sites was supported by the unique opioid meptazinol, which selectively bound to mu 1 sites. As expected from its mu 1 binding selectivity, its analgesic actions in the mouse, localized supraspinally, were antagonized by the selective mu 1 antagonist naloxonazine and it had no respiratory depressant actions. Other binding studies suggested the presence of discrete SKF10,047-selective (KD approximately 5 nM) binding sites in rat brain which differed from both kappa sites and the previously reported PCP-binding sigma sites. Additional binding and autoradiographical studies have also implied the presence of beta-endorphin, or epsilon, sites in the CNS.
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PMID:Biochemical and pharmacological evidence for opioid receptor multiplicity in the central nervous system. 631 56

We report a case of Pneumocystis carinii pneumonia in a patient with ectopic production of adrenocorticotropic hormone (ACTH). The patient presented with Cushing's syndrome caused by a malignant thymic carcinoid. Pneumocystis carinii pneumonia should be considered in the differential diagnosis of pneumonia in patients with endogenous Cushing's syndrome.
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PMID:Endogenous Cushing's syndrome complicated by Pneumocystis carinii pneumonia. 660 98


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