Endogenous opioids and related peptides: from molecular biology to clinical medicine The Sir Henry Dale Lecture for 1985

1985 ◽  
Vol 107 (2) ◽  
pp. 147-157 ◽  
Author(s):  
H. Imura ◽  
Y. Kato ◽  
Y. Nakai ◽  
K. Nakao ◽  
I. Tanaka ◽  
...  

ABSTRACT Advances in techniques in molecular biology have facilitated the research into endogenous opioids and related peptides in several ways. The organization and expression of genes and the primary structure of three precursor proteins of opioid peptides have been elucidated. These studies predicted the presence of potentially bioactive peptides, which has been confirmed by later studies. Advances in techniques in protein chemistry have helped to elucidate the distribution and molecular forms of endogenous opioids and related peptides in the body, and the processing of precursor proteins. Studies on the function of these peptides have shown a broad spectrum of actions. Leumorphin, a newly identified peptide, has been shown to exhibit unique biological activities. In spite of extensive studies, the physiological and pathophysiological significance of opioid peptide systems are not yet completely understood. This is mainly due to the paucity of our knowledge about opioid receptors. Further studies on the subtypes of opioid receptors will help to elucidate all aspects of the function of endogenous opioids and related peptides. J. Endocr. (1985) 107, 147–157

2010 ◽  
Vol 22 (1) ◽  
pp. 224 ◽  
Author(s):  
R. Minoia ◽  
T. Q. Dang-Nguyen ◽  
K. Matsukawa ◽  
M. Kaneda ◽  
M. E. Dell'Aquila ◽  
...  

Embryonic stem cells can become any tissue in the body, excluding a placenta. Growth factors, hormones, and neurotransmitters have been implicated in the regulation of their fate. Because various neural precursors express functional neurotransmitter receptors, as G-protein-coupled receptors, it is anticipated that they are involved in cell fate decisions. Moreover, a high level of endogenous opioids linked to G-protein-coupled receptor above all μ opioid receptors (MOR) has been shown to interfere with normal calcium metabolism and with the activity of the mitogen-activated protein kinase (MAPK). Thus it is very important to understand the possible influence of opioid activities in the regulation of stem cell fate. In this study we investigated the presence of MOR on porcine in vitro-produced embryos at one-cell, 4-cell, morula, and blastocyst stages by immunostaining. The COC were collected by aspiration, cultured in NCSU-37 medium supplemented with hormones for 20 to 22 h, and then in maturation medium without hormones for 24 h. After this time, COC were inseminated with frozen-thawed epididymal spermatozoa at the concentration of 10 × 5 sperm cells mL-1 for 3 h. After removal of cumulus cells, putative zygotes were cultured in IVC Pyr-Lac medium for the first 2 days and in IVC Glu medium until Day 6 (the day of IVF was defined as Day 0). Embryos at different stages were collected at 12, 36, 120, and 144 h post fertilization, and kept in 4% (v/v) paraformaldehyde until examination. All samples were washed and incubated for 30 min in PBS-1%BSA. Controls were incubated in PBS-1% BSA for 90 min, whereas embryos were incubated with a 1 : 2500 dilution of the primary rabbit antibody against the third extracellular loop of MOR. Prior to examination, all samples were washed in PBS and incubated with a FITC-conjugated anti rabbit IgG-secondary antibody diluted 1:200 in Evans Blue/PBS1x. Samples were visualized by laser scanning confocal microscope (Nikon). The immunofluorescence localize, by intense brilliant green, the presence of MOR on blastomers of all stage embryos examined, whereas the embryos of negative control did not show any fluorescent region or spotted coloring. Our results support specific implication of the opioid receptors in developmental process of porcine embryos. Their presence suggests a possible role of MOR in embryonic development. Thus it can be speculated that there is a role for MOR in controlling key events of the stem cell life. However, these primary results must be confirmed by the demonstration of protein expression (by Western blot) of MOR in the embryos and deeply studied to understand the exact functional role of MOR in them at this level. JSPS short-term scholarship.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1008-1008
Author(s):  
B. Bandelow ◽  
C. Schmahl ◽  
P. Falkai ◽  
D. Wedekind

The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems have been discussed, including serotoninergic, dopaminergic, and other neurotransmitter systems.Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD.1 The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target μ-opioid receptors. Self-injury, food-restriction, aggressive behavior, and sensation-seeking may be interpreted as a desperate attempt to artificially set the body to “survival mode”, in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with μ-opioid receptor antagonists.An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder.


2019 ◽  
Vol 30 (3) ◽  
pp. 16-22

World Health Organization (WHO) estimated that 80% of the population of developing countries use traditional medicines, mostly natural plant products, for their primary health care needs. In the past few decades, the medicinal value of plants has been assumed more important dimension owing largely to the discovery that extracts from plants contain not only primary metabolites but also a diverse array of secondary metabolites with antioxidant potential. Medicinal plants are potential sources of natural compounds with biological activities and therefore attract the attention of researchers worldwide. Antioxidants are vital substances which possess ability to protect the body from damage due to free radical-induced oxidative stress. The purpose of current study was to determine the antioxidant activities and bioactive components of Foeniculum vulgare (fennel) (Samonsabar) seeds by using UV Visible Spectrophotometer (UV-Vis) and Gas Chromatography-Mass Spectrometry (GC-MS). Aqueous extract of fennel seeds showed more antioxidant activity (IC50: 0.28 ug/ml) than ethanolic extract (IC50: 0.83 ug/ml) and comparable to standard antioxidant, ascorbic acid (IC50: 0.59 ug/ml). GC-MS analysis was fruitful in identification of compounds based on peak area, retention time, molecular formula, molecular weight, MS Fragmentions and pharmacological actions. Ten bioactive phytochemical compounds from aqueous extracts and 11 from ethanolic extract of fennel seeds were identified. These findings indicated that fennel seeds are potential to provide preventive properties against oxidative damage. These results will give scientific information for quality control of indigenous drug to herbal medicine users and local practitioners using fennel for different types of ailments


Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 79
Author(s):  
Svetlana N. Morozkina ◽  
Thi Hong Nhung Vu ◽  
Yuliya E. Generalova ◽  
Petr P. Snetkov ◽  
Mayya V. Uspenskaya

For a long time, the pharmaceutical industry focused on natural biologically active molecules due to their unique properties, availability and significantly less side-effects. Mangiferin is a naturally occurring C-glucosylxantone that has substantial potential for the treatment of various diseases thanks to its numerous biological activities. Many research studies have proven that mangiferin possesses antioxidant, anti-infection, anti-cancer, anti-diabetic, cardiovascular, neuroprotective properties and it also increases immunity. It is especially important that it has no toxicity. However, mangiferin is not being currently applied to clinical use because its oral bioavailability as well as its absorption in the body are too low. To improve the solubility, enhance the biological action and bioavailability, mangiferin integrated polymer systems have been developed. In this paper, we review molecular mechanisms of anti-cancer action as well as a number of designed polymer-mangiferin systems. Taking together, mangiferin is a very promising anti-cancer molecule with excellent properties and the absence of toxicity.


2017 ◽  
Vol 32 (1) ◽  
pp. 444-451 ◽  
Author(s):  
Adriano Mollica ◽  
Sveva Pelliccia ◽  
Valeria Famiglini ◽  
Azzurra Stefanucci ◽  
Giorgia Macedonio ◽  
...  

Endocrinology ◽  
2004 ◽  
Vol 145 (3) ◽  
pp. 1331-1341 ◽  
Author(s):  
Shaaban A. Mousa ◽  
Mehdi Shakibaei ◽  
Nicolle Sitte ◽  
Michael Schäfer ◽  
Christoph Stein

Abstract The opioid peptide β-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.


Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 423 ◽  
Author(s):  
Yadollah Bahrami ◽  
Wei Zhang ◽  
Christopher M. M. Franco

Sea cucumbers are an important ingredient of traditional folk medicine in many Asian countries, which are well-known for their medicinal, nutraceutical, and food values due to producing an impressive range of distinctive natural bioactive compounds. Triterpene glycosides are the most abundant and prime secondary metabolites reported in this species. They possess numerous biological activities ranging from anti-tumour, wound healing, hypolipidemia, pain relieving, the improvement of nonalcoholic fatty livers, anti-hyperuricemia, the induction of bone marrow hematopoiesis, anti-hypertension, and cosmetics and anti-ageing properties. This study was designed to purify and elucidate the structure of saponin contents of the body wall of sea cucumber Holothuria lessoni and to compare the distribution of saponins of the body wall with that of the viscera. The body wall was extracted with 70% ethanol, and purified by a liquid-liquid partition chromatography, followed by isobutanol extraction. A high-performance centrifugal partition chromatography (HPCPC) was conducted on the saponin-enriched mixture to obtain saponins with a high purity. The resultant purified saponins were analyzed using MALDI-MS/MS and ESI-MS/MS. The integrated and hyphenated MS and HPCPC analyses revealed the presence of 89 saponin congeners, including 35 new and 54 known saponins, in the body wall in which the majority of glycosides are of the holostane type. As a result, and in conjunction with existing literature, the structure of four novel acetylated saponins, namely lessoniosides H, I, J, and K were characterized. The identified triterpene glycosides showed potent antifungal activities against tested fungi, but had no antibacterial effects on the bacterium Staphylococcus aureus. The presence of a wide range of saponins with potential applications is promising for cosmeceutical, medicinal, and pharmaceutical products to improve human health.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 523
Author(s):  
Xiang Li ◽  
Yan Xin ◽  
Yuqian Mo ◽  
Pavel Marozik ◽  
Taiping He ◽  
...  

Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5–2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.


Author(s):  
Nur Mujaddidah Mochtar

Background: There are various circumstances where measurements are not actually possible, replacement parameters can be used to estimate body height. Many characteristics of body height measurement and how to measure it. These include anthropometric measurements that can be used for the identification of medicolegal-forensic processes. Body height in clinical medicine and in the field of scientific research can be easily estimated using various anthropometric parameters such as arm span, knee height, foot length and foot breadth, and others. The arm span and foot length has proved to be one of the most reliable predictors. This study was conducted to estimate of body height from arm span and foot length using the regression equation and to determine the correlation between the body height and arm span and foot length.Methods: This study was conducted at Universitas Muhammadiyah Surabaya with 182 Javanese female students. Stature, arm span and foot length measured directly using anthropometric technique and measuring tape. The data obtained were then analyzed with SPSS version 16. The regression equation was derived for the estimate of body height and the relationship between stature, arm span and foot length determined by the Pearson correlation.               Results: We found that the mean body height of Javanese women was 1534,45 ± 47,623  mm, mean of arm span 1543,25 ± 60,468 mm and the mean of foot length 226,14 ± 9,586 mm. The correlation between stature and arm span was positive and significant (r = 0,715  , p <0,05). The correlation between stature and foot length was positive and significant (r = 0,726 , p <0,05). The correlation between stature and arm span and foot length was positive and significant (r = 0,798, p <0,05).               Conclusion: Body height correlates well with the arm span and foot length so that it can be used as a reliable marker for high estimates using regression equations.


Sign in / Sign up

Export Citation Format

Share Document