Strategies to Improve Bioavailability and In Vivo Efficacy of the Endogenous Opioid Peptides Endomorphin-1 and Endomorphin-2

2015 ◽  
Vol 16 (2) ◽  
pp. 141-155 ◽  
Author(s):  
Rossella De Marco ◽  
Anna Janecka
Keyword(s):  
Opioid Peptides ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
In Vivo Efficacy

Effects of porcine relaxin on oxytocin release from the neurohypophysis in the anaesthetized lactating rat

1986 ◽  
Vol 109 (3) ◽  
pp. 393-397 ◽  
Author(s):  
K. T. O'Byrne ◽  
L. Eltringham ◽  
G. Clarke ◽  
A. J. S. Summerlee
Keyword(s):  
Opioid Peptides ◽  
Inhibitory Effect ◽  
Opioid Antagonist ◽  
Dependent Manner ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Oxytocin Release ◽  
Relaxin 2

ABSTRACT The effect of relaxin on electrically evoked release of oxytocin from the posterior pituitary was examined by monitoring changes in intramammary pressure in the anaesthetized lactating rat. The amount of oxytocin released by electrical stimulation of the neurohypophysis in vivo was dramatically reduced following i.v. injection of highly purified porcine relaxin (2·5–10 μg/rat). Relaxin inhibited oxytocin release in a dose-dependent manner and the onset of inhibition occurred within 6–10 min and lasted for 10–60 min. No effect on the sensitivity of the mammary gland to exogenous oxytocin was observed after relaxin treatment. During the period of inhibition, i.v. injection of the opioid antagonist naloxone chloride (1 mg/kg) completely and immediately restored electrically evoked oxytocin release. The neurohypophysis is known to contain endogenous opioid peptides, therefore the effect of relaxin on electrically stimulated release of oxytocin from the rat isolated neural lobe in vitro was examined. Relaxin (500–2000 ng/ml) failed to inhibit oxytocin release in vitro. The results suggest that relaxin can inhibit the release of oxytocin from terminals in the neurohypophysis, but by an indirect mechanism. This action appears to be mediated through endogenous opioid peptides whose source is not clear. They are unlikely to be of neurohypophysial origin and may probably come from the adrenal medulla, since acute adrenalectomy negated the inhibitory effect of relaxin on oxytocin release. J. Endocr. (1986) 109, 393–397

Endogenous opioid peptides modulate the acetylcholine-stimulated release of adrenal catecholamines in vivo

1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S226-S227
Author(s):  
M. DIETRICH ◽  
H. JARRY ◽  
A. BARTHEL ◽  
A. GIESLER ◽  
W. WUTTKE
Keyword(s):  
Opioid Peptides ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid

Radioendocrine Therapy of Brain Tumors with the Long Acting Opioid Antagonist Naltrexone in Association with Radiotherapy

1993 ◽  
Vol 79 (3) ◽  
pp. 198-201 ◽  
Author(s):  
Paolo Lissoni ◽  
Sofia Meregalli ◽  
Vittorio Fossati ◽  
Sandro Barni ◽  
Gabriele Tancini ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Opioid Peptides ◽  
Tumor Regression ◽  
Malignant Gliomas ◽  
Opioid Antagonist ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Malignant Astrocytomas ◽  
Long Acting

Aims and Background Malignant gliomas remain untreatable as the different therapeutic combinations are generally only palliative. Recent experimental evidence suggests that endogenous opioid peptides are involved in brain tumor growth. The aim of the present study was to evaluate the effect on survival of concomitant administration of the long-acting opioid antagonist naltrexone (NTX) in patients with malignant astrocytomas treated with radiotherapy (RT). Methods 21 patients with high grade malignant gliomas were randomized to receive RT alone or RT plus NTX. The dose of RT was 60 Gy. NTX was given orally at a dose of 100 mg every other day without interruption until disease progression. Results The objective tumor regression rate in patients treated with RT plus NTX was higher than that of those treated with RT alone but not significantly so. On the contrary, the percentage of survivals at 1 year was significantly higher in patients treated with RT plus NTX than in those treated with RT alone (5/10 vs 1/11, P < 0.05). NTX therapy was substantially well tolerated in most patients. Conclusions The finding of longer survival in brain tumor patients treated with RT plus NTX than in those who received RT alone suggests in vivo involvement of endogenous opioid peptides in regulating the growth of malignant astrocytomas.

scholarly journals Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects

2021 ◽  
Vol 118 (16) ◽  
pp. e2000017118
Author(s):  
Ram Kandasamy ◽  
Todd M. Hillhouse ◽  
Kathryn E. Livingston ◽  
Kelsey E. Kochan ◽  
Claire Meurice ◽  
...  
Keyword(s):  
Side Effects ◽  
G Protein ◽  
Opioid Receptor ◽  
Opioid Peptides ◽  
Chinese Hamster ◽  
Mu Opioid Receptor ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Mu Opioid

Positive allosteric modulators (PAMs) of the mu-opioid receptor (MOR) have been hypothesized as potentially safer analgesics than traditional opioid drugs. This is based on the idea that PAMs will promote the action of endogenous opioid peptides while preserving their temporal and spatial release patterns and so have an improved therapeutic index. However, this hypothesis has never been tested. Here, we show that a mu-PAM, BMS-986122, enhances the ability of the endogenous opioid Methionine-enkephalin (Met-Enk) to stimulate G protein activity in mouse brain homogenates without activity on its own and to enhance G protein activation to a greater extent than β-arrestin recruitment in Chinese hamster ovary (CHO) cells expressing human mu-opioid receptors. Moreover, BMS-986122 increases the potency of Met-Enk to inhibit GABA release in the periaqueductal gray, an important site for antinociception. We describe in vivo experiments demonstrating that the mu-PAM produces antinociception in mouse models of acute noxious heat pain as well as inflammatory pain. These effects are blocked by MOR antagonists and are consistent with the hypothesis that in vivo mu-PAMs enhance the activity of endogenous opioid peptides. Because BMS-986122 does not bind to the orthosteric site and has no inherent agonist action at endogenously expressed levels of MOR, it produces a reduced level of morphine-like side effects of constipation, reward as measured by conditioned place preference, and respiratory depression. These data provide a rationale for the further exploration of the action and safety of mu-PAMs as an innovative approach to pain management.

Microdialysis of extracellular endogenous opioid peptides from rat brain in vivo

Neuroscience ◽  
1989 ◽  
Vol 33 (3) ◽  
pp. 549-557 ◽  
Author(s):  
N.T. Maidment ◽  
D.R. Brumbaugh ◽  
V.D. Rudolph ◽  
E. Erdelyi ◽  
C.J. Evans
Keyword(s):  
Rat Brain ◽  
Opioid Peptides ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid

Do Endogenous Opioid Peptides Cause Hepatic Encephalopathy?

1987 ◽  
Vol 72 (s16) ◽  
pp. 90P-91P
Author(s):  
J.R. Thornton ◽  
M.S. Losowsky
Keyword(s):  
Hepatic Encephalopathy ◽  
Opioid Peptides ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid

Met5-enkephalin protects isolated adult rabbit cardiomyocytes via δ-opioid receptors

1999 ◽  
Vol 277 (6) ◽  
pp. H2442-H2450 ◽  
Author(s):  
Yasushi Takasaki ◽  
Roger A. Wolff ◽  
Grace L. Chien ◽  
Donna M. van Winkle
Keyword(s):  
Cell Death ◽  
Opioid Receptors ◽  
Ischemic Preconditioning ◽  
Opioid Peptides ◽  
Trypan Blue ◽  
Adult Rabbit ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Simulated Ischemia ◽  
Hypoxic Incubation

In rats and rabbits, endogenous opioid peptides participate in ischemic preconditioning. However, it is not known which endogenous opioid(s) can trigger cardioprotection. We examined preconditioning-induced and opioid-induced limitation of cell death in isolated, calcium-tolerant, adult rabbit cardiomyocytes. Cells were subjected to simulated ischemia by pelleting and normothermic hypoxic incubation. Preconditioning was elicited with 15 min of simulated ischemia followed by 15 min of resuspension and reoxygenation. All cells underwent 180 min of simulated ischemia. Cell death was assessed by trypan blue permeability. Morphine protected cells, as did preconditioning; naloxone blocked the preconditioning-induced protection. Exogenous Met5-enkephalin (ME) induced protection, but exogenous β-endorphin did not. ME-induced protection was blocked by the δ-selective antagonist naltrindole. Additionally, two other proenkephalin products, Leu5-enkephalin and Met5-enkephalin-Arg-Phe, provided protection equipotent to ME. These data suggest that one or more proenkephalin products interact with δ-opioid receptors to endogenously trigger opioid-mediated protection.

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