Dynorphin Modulates Ocular Hydrodynamics and Releases Atrial Natriuretic Peptide via Activation of κ-Opioid Receptors

Russell, Karen; Potter, David E.

doi:10.1006/exer.2002.2024

Cited by 11 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The apparent incomplete blockade may also be related to the relative contributions of MOR and KOR in modulating pupil dynamics. Whereas MOR agonists are well known to regulate pupil diameter, KORs are known to modulate intraocular pressure ( Russell and Potter, 2002 ; Rasmussen et al, 2007 ). Specifically, KOR agonists reduce intraocular pressure, an effect that is blocked by KOR antagonists ( Russell et al, 2000 ; Russell and Potter, 2002 ; Rasmussen et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas MOR agonists are well known to regulate pupil diameter, KORs are known to modulate intraocular pressure ( Russell and Potter, 2002 ; Rasmussen et al, 2007 ). Specifically, KOR agonists reduce intraocular pressure, an effect that is blocked by KOR antagonists ( Russell et al, 2000 ; Russell and Potter, 2002 ; Rasmussen et al, 2007 ). Therefore, it is conceivable that LY2456302 effects on intraocular pressure may alter the ability of morphine to produce pupillary changes, such that greater occupancy at MOR is required to overcome alterations in pupil dynamics produced by changes in intraocular pressure.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Determining Pharmacological Selectivity of the Kappa Opioid Receptor Antagonist LY2456302 Using Pupillometry as a Translational Biomarker in Rat and Human

Rorick-Kehn

Witcher

Lowe

et al. 2015

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

Background:Selective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression. The kappa opioid receptor antagonist, LY2456302, exhibits ~30-fold higher affinity for kappa opioid receptors over mu opioid receptors, which is the next closest identified pharmacology.Methods:Here, we determined kappa opioid receptor pharmacological selectivity of LY2456302 by assessing mu opioid receptor antagonism using translational pupillometry in rats and humans.Results:In rats, morphine-induced mydriasis was completely blocked by the nonselective opioid receptor antagonist naloxone (3mg/kg, which produced 90% mu opioid receptor occupancy), while 100 and 300mg/kg LY2456302 (which produced 56% and 87% mu opioid receptor occupancy, respectively) only partially blocked morphine-induced mydriasis. In humans, fentanyl-induced miosis was completely blocked by 50mg naltrexone, and LY2456302 dose-dependently blocked miosis at 25 and 60mg (minimal-to-no blockade at 4–10mg).Conclusions:We demonstrate, for the first time, the use of translational pupillometry in the context of receptor occupancy to identify a clinical dose of LY2456302 achieving maximal kappa opioid receptor occupancy without evidence of significant mu receptor antagonism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Determining Pharmacological Selectivity of the Kappa Opioid Receptor Antagonist LY2456302 Using Pupillometry as a Translational Biomarker in Rat and Human

Rorick-Kehn

Witcher

Lowe

et al. 2015

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…Topical application of a selective κ opioid agonist, bremazocine, has been shown to reduce aqueous humor flow rate presumably by increasing atrial natriuretic peptide levels [13], [14], [15]. A second selective κ agonist, spiradoline, was found to increase NO levels in both ciliary and trabecular meshwork cells, an action that would decrease aqueous humor production and increase its outflow [3].…”

Section: Discussionmentioning

confidence: 99%

Influence of the Hypothalamic Arcuate Nucleus on Intraocular Pressure and the Role of Opioid Peptides

Jin

Yuan

2014

PLoS ONE

View full text Add to dashboard Cite

BackgroundAn opioid peptide neuron/humoral feedback regulation might be involved in changes of intraocular pressure (IOP). The aims of this study are to investigate the effects of arcuate nucleus (ARC) and opioid peptides on intraocular pressure (IOP).MethodsFifty-four healthy purebred New Zealand white rabbits (108eyes) were randomly divided into 4 groups, including control group, electrical stimulation group, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) group, and [D-Pen 2, D-Pen5]- enkephalin (DPDPE) group. Bilateral IOP was measured after unilateral electrical stimulation of the ARC or unilateral microinjection into the ARC of the selective μ-opioid receptor agonist DAMGO or the selective δ opioid receptor agonist DPDPE, both alone and after pre-administration of either the non-selective opioid receptor antagonist naloxone or saline.ResultsBoth electrical stimulation in ARC and micro-injection either or opioid receptor agonists, DAMGO or DPDPE, respectively, caused a significant bilateral reduction in IOP (P<0.05) which was more pronounced in the ipsilateral than in the contralateral eye. Pretreatment with naloxone prevented some, but not all IOP reductions.ConclusionThe ARC takes part in the negative regulation of IOP, an action that may involve opioid neurons.

show abstract

“…In the eye, experimental and/or clinical evidence has suggested key roles of endogenous opioids and their receptors in the regulation of iris function, accommodative power, aqueous humor dynamics, corneal wound healing, retinal development, and retinal neuroprotection. [3][4][5][24][25][26][27][28] For example, an endogenous peptide ligand for DOR, enkephalin, has been shown to be present in the rat retina. 28 Although opioids have been demonstrated to alter a variety of ocular functions, the detailed mechanisms by which DOR activation elicits pharmacological actions and subsequently neuroprotection have not been clearly defined in the eye.…”

mentioning

confidence: 99%

Delta Opioids: Neuroprotective Roles in Preclinical Studies

Husain

2018

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Since ancient times, opioids have been used clinically and abused recreationally. In the early stages (about 1,000 AD) of opium history, an Arab physician, Avicenna, administered opioids to control diarrhea and eye diseases. Opioids have very strong pain relieving properties and they also regulate numerous cellular responses. Opioid receptors are expressed throughout the body, including the nervous system, heart, lungs, liver, gastrointestinal tract, and retina. Delta opioid receptors (DORs) are a very attractive target from the perspective of both receptor function and their therapeutic potential. Due to a rapid progress in mouse mutagenesis and development of small molecules as DOR agonist, novel functions and roles of DORs have emerged in recent years. This review article focuses on the recent advances in the neuroprotective roles of DOR agonists in general and retina neuroprotection in particular. Rather than being exhaustive, this review highlights the selected studies of DOR function in neuroprotection. We also highlight our preclinical studies using rodent models to demonstrate the potentials of DOR agonists for retinal neuroprotection. Based on existing literature and our recently published data on the eye, DOR agonists possess therapeutic abilities that protect the retina and optic nerve injury against glaucoma and perhaps other retinopathies as well. This review also highlights the signaling events associated with DOR for neuroprotection in the eye. There is a need for translational research on DORs to recognize their potential for clinical application such as in glaucoma.

show abstract

Dynorphin Modulates Ocular Hydrodynamics and Releases Atrial Natriuretic Peptide via Activation of κ-Opioid Receptors

Cited by 11 publications

References 38 publications

Determining Pharmacological Selectivity of the Kappa Opioid Receptor Antagonist LY2456302 Using Pupillometry as a Translational Biomarker in Rat and Human

Determining Pharmacological Selectivity of the Kappa Opioid Receptor Antagonist LY2456302 Using Pupillometry as a Translational Biomarker in Rat and Human

Influence of the Hypothalamic Arcuate Nucleus on Intraocular Pressure and the Role of Opioid Peptides

Delta Opioids: Neuroprotective Roles in Preclinical Studies

Contact Info

Product

Resources

About