scholarly journals Kappa opioid receptor (KOR) signaling on peripheral sensory neurons in vitro and in vivo

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Matthew Rowan ◽  
Teresa Sanchez ◽  
Yamille Silva ◽  
Blaine McGuire ◽  
William Clarke ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Sensory Neurons ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Peripheral Sensory Neurons ◽  
Peripheral Sensory

scholarly journals Regulation of κ-Opioid Receptor Signaling in Peripheral Sensory Neurons In Vitro and In Vivo

2011 ◽  
Vol 338 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Kelly A. Berg ◽  
Matthew P. Rowan ◽  
Teresa A. Sanchez ◽  
Michelle Silva ◽  
Amol M. Patwardhan ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Sensory Neurons ◽  
Receptor Signaling ◽  
Peripheral Sensory Neurons ◽  
Peripheral Sensory

scholarly journals Functional Selectivity of Kappa Opioid Receptor Agonists in Peripheral Sensory Neurons

2015 ◽  
Vol 355 (2) ◽  
pp. 174-182 ◽  
Author(s):  
Raehannah J. Jamshidi ◽  
Blaine A. Jacobs ◽  
Laura C. Sullivan ◽  
Teresa A. Chavera ◽  
Rachel M. Saylor ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Sensory Neurons ◽  
Kappa Opioid Receptor ◽  
Functional Selectivity ◽  
Kappa Opioid ◽  
Receptor Agonists ◽  
Peripheral Sensory Neurons ◽  
Peripheral Sensory ◽  
Opioid Receptor Agonists

scholarly journals Signaling characteristics and functional regulation of delta opioid-kappa opioid receptor (DOP-KOP) heteromers in peripheral sensory neurons

2019 ◽  
Vol 151 ◽  
pp. 208-218 ◽  
Author(s):  
Blaine A. Jacobs ◽  
Miryam M. Pando ◽  
Elaine M. Jennings ◽  
Raehannah J. Jamshidi ◽  
Joshua C. Zamora ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Sensory Neurons ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Peripheral Sensory Neurons ◽  
Functional Regulation ◽  
Peripheral Sensory

scholarly journals Regulation of kappa Opioid Receptor (KOR) Responsiveness on Peripheral Sensory Neurons

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Teresa A Sanchez ◽  
Matthew P Rowan ◽  
Michelle Silva ◽  
William P Clarke ◽  
Kelly A Berg
Keyword(s):  
Opioid Receptor ◽  
Sensory Neurons ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Peripheral Sensory Neurons ◽  
Peripheral Sensory

scholarly journals Tackling the opioid crisis - development of kappa-opioid receptor peptide agonists for safer analgesic therapy

2021 ◽  
Author(s):  
Rink-Jan Lohman ◽  
Karnaker Reddy Tupally ◽  
Ajit Kandale ◽  
Peter Cabot ◽  
Harendra Parekh
Keyword(s):  
Side Effects ◽  
Opioid Receptor ◽  
Specific Activity ◽  
Opioid Analgesic ◽  
Kappa Opioid Receptor ◽  
Metabolic Stability ◽  
Clinical Translation ◽  
Kappa Opioid

The kappa opioid receptor (KOPr) has exceptional potential as an analgesic target, seemingly devoid of the many peripheral side-effects of Mu receptors. Kappa-selective, small molecule pharmaceutical agents have been developed, but centrally mediated side effects have the limited their clinical translation. Here, we modify an active endogenous Dynorphin peptide with the aim of improving drug-likeness and developing safer KOPr agonists for clinical use. Using rational, iterative design and modern peptide chemistry, we developed a series of potent, selective and metabolically stable peptides from Dynorphin 1-7. Peptides were assessed for cAMP-modulation against Kappa, Mu and Delta opioid receptors, metabolic stability, KOPr specificity and binding, and interrogated for in vitro desensitisation and pERK signalling capability. Finally, lead peptides were evaluated for efficacy in Freund’s complete adjuvant rat model of inflammatory nociception. A library of 70 peptides was synthesised and assessed for pharmacological and metabolic stability factors. At least 10 peptide candidates showed low nanomolar activity (˂50 nM) in a cAMP assay, specificity for KORr, and plasma half-life >60 min, with 6 candidates also stable in trypsin. None of the selected peptides showed pERK activity, with a bias towards cAMP signalling. In vivo, KA305 and KA311 showed anti-nociception opioid receptor-specific activity comparable to morphine and U50 844. These highly potent and metabolically stable peptides are promising opioid analgesic leads for clinical translation. Since they are biased peptide KOPr agonists, it is plausible they lack many of the most significant side effects, such as tolerance, addiction, sedation and euphoria/dysphoria, common to opioid analgesics.

Signaling Properties of Structurally Diverse Kappa Opioid Receptor Ligands: Toward in Vitro Models of in Vivo Responses

2019 ◽  
Vol 10 (8) ◽  
pp. 3590-3600 ◽  
Author(s):  
Amelia D. Dunn ◽  
Brian Reed ◽  
Jose Erazo ◽  
Ariel Ben-Ezra ◽  
Mary Jeanne Kreek
Keyword(s):  
Opioid Receptor ◽  
In Vitro Models ◽  
Kappa Opioid Receptor ◽  
Receptor Ligands ◽  
Kappa Opioid ◽  
Opioid Receptor Ligands
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