Analogues of cholecystokinin 26–33 selective for B-type CCK receptors possess δ opioid receptor agonist activity in vitro and in vivo: Evidence for similarities in CCK-B and δ opioid receptor requirements

Peptides ◽  
1994 ◽  
pp. 669-671 ◽  
Author(s):  
V. J. Hruby ◽  
S. N. Fang ◽  
T. H. Kramer ◽  
P. Davis ◽  
D. Parkhurst ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Agonist Activity ◽  
Cck Receptors ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

scholarly journals Identification of a Novel Delta Opioid Receptor Agonist Chemotype with Potential Negative Allosteric Modulator Capabilities

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7236
Author(s):  
Yazan J. Meqbil ◽  
Hongyu Su ◽  
Robert J. Cassell ◽  
Kendall L. Mores ◽  
Anna M. Gutridge ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Clinical Drug Development ◽  
In Vitro Characterization ◽  
Opioid Receptor Agonist ◽  
Negative Allosteric Modulator ◽  
Δ Opioid Receptor ◽  
Clinical Drug

The δ-opioid receptor (δOR) holds great potential as a therapeutic target. Yet, clinical drug development, which has focused on δOR agonists that mimic the potent and selective tool compound SNC80 have largely failed. It has increasingly become apparent that the SNC80 scaffold carries with it potent and efficacious β-arrestin recruitment. Here, we screened a relatively small (5120 molecules) physical drug library to identify δOR agonists that underrecruit β-arrestin, as it has been suggested that compounds that efficaciously recruit β-arrestin are proconvulsant. The screen identified a hit compound and further characterization using cellular binding and signaling assays revealed that this molecule (R995045, compound 1) exhibited ten-fold selectivity over µ- and κ-opioid receptors. Compound 1 represents a novel chemotype at the δOR. A subsequent characterization of fourteen analogs of compound 1, however did not identify a more potent δOR agonist. Computational modeling and in vitro characterization of compound 1 in the presence of the endogenous agonist leu-enkephalin suggest compound 1 may also bind allosterically and negatively modulate the potency of Leu-enkephalin to inhibit cAMP, acting as a ‘NAM-agonist’ in this assay. The potential physiological utility of such a class of compounds will need to be assessed in future in vivo assays.

In vivo and in vitro evaluation of novel μ-opioid receptor agonist compounds

2015 ◽  
Vol 767 ◽  
pp. 193-200 ◽  
Author(s):  
Yoshiaki Nikaido ◽  
Aya Kurosawa ◽  
Hitomi Saikawa ◽  
Satoshi Kuroiwa ◽  
Chiharu Suzuki ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
In Vitro Evaluation ◽  
Opioid Receptor Agonist ◽  
Μ Opioid Receptor

scholarly journals In vivo effects of μ-opioid receptor agonist/δ-opioid receptor antagonist peptidomimetics following acute and repeated administration

2018 ◽  
Vol 175 (11) ◽  
pp. 2013-2027 ◽  
Author(s):  
Jessica P Anand ◽  
Kelsey E Kochan ◽  
Anthony F Nastase ◽  
Deanna Montgomery ◽  
Nicholas W Griggs ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Repeated Administration ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Agonist ◽  
Μ Opioid Receptor ◽  
Δ Opioid Receptor ◽  
In Vivo Effects

In vitro and in vivo activity of cyclopeptide Dmt-c[ d -Lys-Phe-Asp]NH 2 , a mu opioid receptor agonist biased toward β-arrestin

Peptides ◽  
2018 ◽  
Vol 105 ◽  
pp. 51-57 ◽  
Author(s):  
Katarzyna Gach-Janczak ◽  
Justyna Piekielna-Ciesielska ◽  
Anna Adamska-Bartłomiejczyk ◽  
Karol Wtorek ◽  
Federica Ferrari ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Opioid Receptor Agonist

scholarly journals Julius H. Comroe Distinguished Lecture: Interdependence of neuromodulators in the control of breathing

2018 ◽  
Vol 125 (5) ◽  
pp. 1511-1525 ◽  
Author(s):  
Hubert V. Forster
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
American Physiological Society ◽  
Receptor Antagonists ◽  
Compensatory Mechanisms ◽  
Opioid Receptor Agonist ◽  
Neurokinin 1 ◽  
G Protein Coupled

In vitro and in vivo anesthetized studies led to the conclusion that “deficiencies in one neuromodulator are immediately compensated by the action of other neuromodulators,” which suggests an interdependence among neuromodulators. This concept was the focus of the 2018 Julius H. Comroe Lecture to the American Physiological Society in which I summarized our published studies testing the hypothesis that if modulatory interdependence was robust, breathing would not decrease during dialysis of antagonists to G protein-coupled excitatory receptors or agonists to inhibitory receptors into the ventral respiratory column (VRC) or the hypoglossal motor nuclei (HMN). We found breathing was not decreased during unilateral VRC dialyses of antagonists to excitatory muscarinic, serotonergic, and neurokinin-1 receptors alone or in combinations nor was breathing decreased with unilateral VRC dialysis of a µ-opioid receptor agonist. Analyses of the effluent dialysate revealed locally increased serotonin (excitatory) during muscarinic receptor blockade and decreased γ-aminobutyric acid (inhibitory) during dialysis of opioid agonists, suggesting an interdependence of neuromodulators through release of compensatory neuromodulators. Bilateral dialysis of receptor antagonists or agonist in the VRC increased breathing, which does not support the concept that unchanged breathing with unilateral dialyses was due to contralateral compensation. In contrast, in the HMN neither unilateral nor bilateral dialysis of the excitatory receptor antagonists altered breathing, but unilateral dialysis of the opioid receptor agonist decreased breathing. We conclude: 1) there is site-dependent interdependence of neuromodulators during physiologic conditions, and 2) attributing physiologic effects to a specific receptor perturbation is complicated by local compensatory mechanisms.

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