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)

Acute cocaine administration alters secretion of anterior pituitary hormones in experimental animals, and cocaine abuse may compromise neuroendocrine function in humans. The goal of this study was to examine cocaine's acute effects on neuroendocrine hormones in cocaine-dependent men. Plasma adrenocorticotropic hormone (ACTH), luteinizing hormone and prolactin levels were measured in 18 men before and after i.v. administration of cocaine (30 mg) or placebo. Each subject served as his own control during the i.v. placebo and cocaine administration conditions. Plasma cocaine levels peaked at 260 ng/ml within 5 min after the i.v. injection. Plasma ACTH levels increased significantly above base-line levels at 5, 15, 30 (P < .01) and 45 min (P < .05) after i.v. cocaine. Plasma luteinizing hormone levels increased significantly above base-line levels at 5 (P < .05) and at 15 min (P < .01) after i.v. cocaine. No changes in plasma ACTH or luteinizing hormone levels were found after i.v. placebo injection. Plasma prolactin levels decreased significantly at 30, 45, 60, 90 and 120 min (P < .01) after both i.v. cocaine and placebo administration. Cocaine-induced increases in plasma ACTH levels may be due to its effects on dopaminergic systems which modulate corticotropin-releasing factor release in brain.
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PMID:Acute effects of cocaine on plasma adrenocorticotropic hormone, luteinizing hormone and prolactin levels in cocaine-dependent men. 133 1

Cocaine is reported to be immunotoxic. The biochemical mechanisms responsible for the immunopharmacological outcomes of cocaine in vivo and in vitro remain, however, to be fully elucidated. Our experimental data confirm that exposure of normal human T cells to micromolar concentrations of cocaine modulates T-cell responses to stimulation by a variety of stimuli, and indicate that cocaine impairs early activation events during CD4+ but not CD4- T-cell stimulation. Pre-incubation of enriched CD4+ T-cell subpopulations that express the homing receptor CD62L with nanomolar concentrations of the endogenous opioid peptide beta-endorphin leads to a more severe impairment of activation than that noted following pre-incubation with micromolar concentrations of cocaine alone. These findings begin to elucidate the molecular and cellular mechanisms of the immunopathology of cocaine. Our data support the proposition that cocaine abuse may place cocaine-abuser HIV-seropositive individuals at increased risk of opportunistic infections.
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PMID:Cocaine blunts human CD4+ cell activation. 785 54

Previous in vivo studies revealed that the mixed agonist-antagonist buprenorphine can down-regulate mu and up-regulate delta 2 and kappa 1 opioid receptors in rat brain. In this report brain regional differences in opioid receptor adaptation were addressed. Rats received i.p. injections with buprenorphine (0.5-2.5 mg/kg) and were killed 20 h later. Membranes from 7 brain regions were analyzed for mu (3H-[D-Ala2,N-mephe4,Gly-ol5] enkephalin), kappa 1 (3H-U-69593), delta 1 (3H-[D-Pen2, D-Pen5] enkephalin) and delta 2 (3H-deltorphin II) receptor binding parameters. Buprenorphine induced down-regulation of mu receptors in frontal cortex, occipital cortex, thalamus, hippocampus, striatum and brain stem. Kd values for 3H-[D-Ala2,N-mephe4,Gly-ol5] enkephalin were unchanged from controls. Up-regulation of kappa 1 receptors was observed in frontal, parietal, occipital cortexes and striatum. Binding to delta 2 sites was elevated in frontal and parietal cortexes. Buprenorphine did not alter delta 1 binding in any of the regions examined. Changes in opioid receptor adaptation induced by buprenorphine were further supported by data from cross-linking of 125I-beta-endorphin to cortical membrane preparations. A reduction in a 60- to 65-kDa band was detected in frontal and occipital cortices in which binding assays revealed down-regulation of mu receptors. In parietal cortex neither the 60- to 65-kDa product nor Bmax changes were observed. These results indicate that buprenorphine is a useful tool to study brain opioid receptor adaptation in vivo and the information accrued may be relevant to the mode of action of this drug in the treatment of heroin and cocaine abuse.
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PMID:Buprenorphine differentially alters opioid receptor adaptation in rat brain regions. 866 93

Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinical and preclinical studies, but the temporal sequence of cocaine-induced changes in other hormones and affective states is unclear. The purpose of this study was to analyze the pattern and temporal concordance of cocaine-induced changes in ACTH, cortisol, dihydroepiandrosterone (DHEA), epinephrine, heart rate and subjective reports of euphoria. Six healthy men who met Diagnostic and Statistical Manual-IV (DSM-IV) criteria for cocaine abuse provided informed consent for participation. Cocaine (0.4 mg/kg) or saline placebo was infused intravenously over 1 min under double-blind conditions. Euphoria, ACTH, epinephrine and heart rate increased significantly within 8 to 12 min after i.v. cocaine administration in all subjects (P<0.01-0.001). Moreover, the increases in euphoria, ACTH, epinephrine and heart rate each were significantly correlated with increases in plasma cocaine levels (P<0.001). Euphoria increased significantly within 2 min after i.v. cocaine injection, as plasma cocaine levels were increasing, and peak euphoria was reported at 10 min (P<0.001). Peak ACTH values were measured at 8.7 (+/-0.8) min after cocaine injection (P<0.01). Peak levels of epinephrine were measured at 10 (+/-1) min after cocaine injection (P<0.05). Peak increases in heart rate occurred at 11.7 (+/-1.1) min after cocaine injection (P<0.05). Peak levels of cortisol and DHEA were measured at 36 (+/-4.0) and 28.7 (+/-4.3) min after cocaine injection (P<0.01 and P<0.01). The temporal concordance between cocaine-induced stimulation of ACTH, epinephrine and subjective euphoria suggests that these hormonal changes are significant concomitants of the abuse-related effects of cocaine. The similarities between these hormonal profiles, the subjective effects of cocaine and the effects of "stress" are discussed.
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PMID:Temporal concordance of cocaine effects on mood states and neuroendocrine hormones. 1175 Jul 70

Cocaine is a highly addictive substance abused worldwide. Its mechanism of action involves initially inhibition of neuronal monoamine transporters in precise brain structures and primarily the dopamine reuptake system located on mesolimbic neurons. Cocaine rapidly increases the dopaminergic neurotransmission and triggers adaptive changes in numerous neuronal circuits underlying reinforcement, reward, sensitization and the high addictive potential of cocaine. Current therapeutic strategies focus on counteracting the cocaine effects directly on the dopamine transporter, through post-synaptic D(1), D(2) or D(3) receptors or through the glutamatergic, serotoninergic, opioid or corticotropin-releasing hormone systems. However, cocaine administration also results in the activation of numerous particular targets. Among them, the sigma(1) (sigma(1)) receptor is involved in several acute or chronic effects of cocaine. The present review will first bring concise overviews of the present strategies followed to alleviate cocaine addiction and animal models developed to analyze the pharmacology of cocaine addiction. Evidence involving activation of the sigma(1) receptor in the different aspects of cocaine abuse, will then be detailed, following acute, repeated, or overdose administration. The therapeutic potentials and neuropharmacological perspectives opened by the use of selective sigma(1) receptor antagonists in cocaine addiction will finally be discussed.
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PMID:Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine addiction and toxicity. 1220 95

Previous reports indicate that prenatal cocaine exposure alters specific behaviors and hypothalamic-pituitary-adrenal axis (HPA) function in the offspring. In most previous studies, cocaine was given via subcutaneous injections. However intravenous administration more closely mimics human cocaine abuse during pregnancy. Therefore, we investigated the effects of prenatal cocaine exposure via intravenous injection to the mothers on open field behavior and HPA axis function of the offspring. We hypothesized that prenatal cocaine exposure decreases immobility in a novel environment, and enhances the HPA response to stress. Dams received cocaine (COC) or vehicle (control, CON) intravenously from gestation day 8 to postnatal day (PD) 5. Behaviors were recorded in the open field on PD 28 (weanlings). As expected, perinatally cocaine-exposed offspring spent less time immobile and had a longer latency to entering the center zone. No other behavioral activities were different between the groups. On PD 43-50, adolescent male and female offspring received either corticotropin releasing hormone (CRH) or saline intravenously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined before, and up to 60 min after injection. COC-exposed offspring of both sexes had higher basal CORT levels. Prenatal cocaine enhanced the CORT response to CRH/saline injections up to 60 min in males but not in females. These novel results show that perinatal administration of cocaine in a manner that most closely mimics human cocaine use has long-term effects on the offspring's behavioral response to stress and on HPA axis functions.
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PMID:Effects of perinatal cocaine exposure on open field behavior and the response to corticotropin releasing hormone (CRH) in rat offspring. 2107 83

Neurochemical differences in the hypothalamic-pituitary axis between individuals and between ages may contribute to differential susceptibility to cocaine abuse. This study measured peptide levels in the pituitary gland (Pit) and lateral hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have previously been characterized for acute locomotor responses to cocaine. Individual peptide profiles were analyzed using mass spectrometric profiling and principal component analysis. Sequences of assigned peptides were verified by tandem mass spectrometry. Principal component analysis classified all strains according to their distinct peptide profiles in Pit samples from adolescent mice, but not adults. Select pro-opiomelanocortin-derived peptides were significantly higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A subset of peptides in the LH, but not in the Pit, was altered by cocaine in adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in adolescents than adults. Neuropeptides in the LH affected by acute cocaine administration included pro-opiomelanocortin-, myelin basic protein-, and glutamate transporter-derived peptides. The observed peptide differences could contribute to differential behavioral sensitivity to cocaine among strains and ages. Peptides were measured using mass spectrometry (MALDI-TOF) in individual lateral hypothalamus and pituitary samples from four strains and two ages of inbred mice in response to acute cocaine administration. Principal component analyses (PCA) classified the strains according to their peptide profiles from adolescent mice, and a subset of peptides in the lateral hypothalamus was altered by cocaine in adolescents.
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PMID:Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration. 2622 48