Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chicks with cannulae chronically implanted into the III cerebral ventricle, the effects of a single dose (10 micrograms) of beta-endorphin on GABA and free glutamic acid content, GAD and GABA-T activities in the diencephalon, brain-stem and brain hemispheres were studied at the time of maximal behavioural stuporous state and analgesia. A significant decrease in GABA concentration both in the diencephalon and brain-stem, accompanied by a significant increase in GABA-T activity in the same areas, was shown to occur. No changes were observed in GAD activity and in glutamic acid content in the studied areas of the brain. In conclusion, present experiments suggest that some central effects of a beta-endorphin may be due to an interference with GABA-ergic transmission.
 ...
PMID:Effects of intraventricular beta-endorphin on GABA system in some areas of chick brain. 52 83

Clinical studies demonstrate that the antidepressant efficacy of St John's wort (Hypericum) is comparable to that of tricyclic antidepressants such as imipramine. Onset of efficacy of these drugs occurs after several weeks of treatment. Therefore, we used in situhybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract, and hypericin (an active constituent of St John's wort) on the expression of genes that may be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine (15 mg kg(-1)), Hypericum (500 mg kg(-1)), and hypericin (0.2 mg kg(-1)) given daily by gavage for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 16-22% in the hypothalamic paraventricular nucleus (PVN) and serotonin 5-HT(1A) receptor mRNA by 11-17% in the hippocampus. Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three compounds on gene transcription suggests a shared action on the centers that control HPA axis activity. A second study was performed to assess the effects of long-term imipramine and Hypericum administration on stress-induced changes in gene transcription in stress-responsive circuits. Repeated immobilization stress (2 h daily for 7 days) increased mRNA levels of CRH in the PVN, proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus. It decreased mRNA levels of 5-HT(1A) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Long-term pre-treatment with either imipramine or Hypericum reduced to control levels the stress-induced increases in gene transcription of GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum. The stress-induced decreases in BDNF and 5-HT(1A)mRNA levels were not prevented by either drug. Taken together, these data show: (1) that Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine; and (2) that select stress-induced changes in gene transcription in particular brain areas can be prevented by long-term treatment with either the prototypic tricyclic antidepressant imipramine or the herbiceutical St John's wort. However, imipramine appears to be more effective in blocking stress effects on the HPA axis than the plant extract.
 ...
PMID:St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats. 1152 69

Anxiety is a heterogeneous term encompassing not only state or trait characteristics but also a wide range of pathologies such as generalized anxiety disorders, phobias, panic and obsessive-compulsive disorders, acute stress disorder, and posttraumatic stress disorder. Given that diverse forms of anxiety exist, numerous animal models have been developed, which are considered to be useful in identifying mechanisms underlying anxiety states. Examples of such animal models include paradigms that assess the behavioral response to neurogenic (or painful stimuli) or psychogenic stressors or to cues that had previously been associated with painful stimuli. The present report presents data regarding the impact of stressors on corticotropin-releasing hormone (CRH), and relates these to changes in anxiety-like states. Specifically, we demonstrate that (1) psychogenic stressors influence the in vivo release of CRH at the central nucleus of the amygdala (CeA); (2) although CRH changes within the CeA are exquisitely sensitive to stressors, they are also elicited by positive stimuli; and (3) while treatment with diazepam attenuates behavioral signs of anxiety, the CRH release associated with a stressor is unaffected by the treatment. The position is offered that although release of CRH within the CeA is increased under stressful conditions, it is not a necessary condition for the consequent behavioral expression of anxiety-like reactions, at least not in minimally threatening situations. We suggest that the CRH responses at the CeA may be involved in a preparatory capacity and, as such, may accompany a range of emotionally significant stimuli, be they appetitive or aversive.
 ...
PMID:Differential involvement of amygdaloid CRH system(s) in the salience and valence of the stimuli. 1465 75

Mindfulness-Based interventions have increased in popularity in psychiatry, but the impact of these treatments on disorder-relevant biomarkers would greatly enhance efficacy and mechanistic evidence. If Generalized Anxiety Disorder (GAD) is successfully treated, relevant biomarkers should change, supporting the impact of treatment and suggesting improved resilience to stress. Seventy adults with GAD were randomized to receive either Mindfulness-Based Stress Reduction (MBSR) or an attention control class; before and after, they underwent the Trier Social Stress Test (TSST). Area-Under-the-Curve (AUC) concentrations were calculated for adrenocorticotropic hormone (ACTH) and pro-inflammatory cytokines. MBSR participants had a significantly greater reduction in ACTH AUC compared to control participants. Similarly, the MBSR group had a greater reduction in inflammatory cytokines' AUC concentrations. We found larger reductions in stress markers for patients with GAD in the MBSR class compared to control; this provides the first combined hormonal and immunological evidence that MBSR may enhance resilience to stress.
 ...
PMID:The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder. 2897 4

Introduction: Generalized anxiety disorder (GAD) is a common and disabling psychiatric condition that affects 3% of the population and exacts significant costs to society if untreated. There are numerous treatment options available, but all have side effects, and none are reliably effective; hence, there is a significant need for new medications.Areas covered: The authors reviewed clinical Phase II and III studies listed on the clinicaltrials.gov and clinicaltrialsregister.eu websites, 2007-present. Additional information was gathered from the study sponsor websites and Pubmed. The categories of mechanisms investigated include: modulators of GABAergic or glutamatergic activity; modulators of monoaminergic systems including serotonin, norepinephrine, and dopamine; and modulators of neuropeptide corticotropin release factor.Expert opinion: There are few investigational drugs in the later stages of clinical development. Challenges include high placebo response rates, enrollment of symptomatic volunteers with minimal depressive and anxiety comorbidity, and the lack of a unifying pathophysiological model. Drug developers should consider implementing trial designs such as sequential parallel comparison design to enhance signal detection. Inclusion of depressive comorbidity may also enhance signal detection by reducing placebo-responsivity. More studies examining glutamate-mediated neuroplasticity in GAD are needed.
 ...
PMID:Novel investigational therapeutics for generalized anxiety disorder (GAD). 3160 87