Effects of polar κ receptor agonists designed for the periphery on ATP-induced Ca2+ release from keratinocytes

MedChemComm ◽  
2016 ◽  
Vol 7 (2) ◽  
pp. 317-326 ◽  
Author(s):  
Fabian Galla ◽  
Christian Bourgeois ◽  
Kirstin Lehmkuhl ◽  
Dirk Schepmann ◽  
Michael Soeberdt ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Human Keratinocytes ◽  
Receptor Agonists ◽  
Opioid Receptor Agonist ◽  
Κ Receptor

The very polar pyridylmethyl derivative 5a (log D7.4 = 1.1) represents a potent and selective full κ-opioid receptor agonist (Ki = 0.13 nM, EC50 = 33 nM), which reduced the release of Ca2+-ions into the cytoplasm in human keratinocytes.

Differential Effects of μ-, δ-, and κ-Opioid Receptor Agonists on Mechanosensitive Gastric Vagal Afferent Fibers in the Rat

2000 ◽  
Vol 83 (4) ◽  
pp. 2209-2216 ◽  
Author(s):  
Noriyuki Ozaki ◽  
J. N. Sengupta ◽  
G. F. Gebhart
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Dose Range ◽  
Receptor Agonists ◽  
Afferent Fibers ◽  
Opioid Receptor Agonist ◽  
Resting Activity ◽  
Vagal Afferent ◽  
Δ Opioid Receptor ◽  
Opioid Receptor Agonists

Single-fiber recordings were made from the decentralized right cervical vagus nerve (hyponodosal) of the rat. A total of 56 afferent fibers that responded to gastric distension (GD) were studied: 6 fibers were stimulated by phasic balloon GD, 50 by fluid GD. All fibers gave increasing responses to increasing pressures of GD (5–60 mmHg). The effects of μ-opioid (morphine), δ-opioid (SNC80), and κ-opioid (EMD61,753, U62,066) receptor agonists were tested on responses of afferent fibers to GD. Morphine, administered systemically over a broad dose range (10 μg to 31 mg/kg, cumulative), had no effect on either resting activity or responses of vagal afferent fibers to GD. Similarly, the δ-opioid receptor agonist SNC80 (0.05–3.2 mg/kg) did not affect resting activity or responses to GD. In contrast, cumulative intra-arterial doses of the κ-opioid receptor agonist EMD61,753 or U62,066 dose dependently attenuated afferent fiber responses to GD. Doses producing inhibition to 50% of the control response to GD of EMD61,753 (8.0 mg/kg) and U62,066 (8.8 mg/kg) did not differ. The effect of U62,066 was moderately attenuated by a nonselective dose (4 mg/kg) of naloxone hydrochloride; the κ-opioid receptor-selective antagonist nor-BNI (20 mg/kg) was ineffective. These results demonstrate that κ-, but not μ- or δ-opioid receptor agonists modulate visceral sensation conveyed by vagal afferent fibers innervating the stomach. Given that κ-opioid receptor agonists effects were only modestly antagonized by naloxone and not at all by nor-BNI, the results point to a novel site of action.

scholarly journals Late preconditioning induced by NO donors, adenosine A1 receptor agonists, and δ1-opioid receptor agonists is mediated by iNOS

2005 ◽  
Vol 289 (5) ◽  
pp. H2251-H2257 ◽  
Author(s):  
Yiru Guo ◽  
Adam B. Stein ◽  
Wen-Jian Wu ◽  
Xiaoping Zhu ◽  
Wei Tan ◽  
...  
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Coronary Occlusion ◽  
Critical Role ◽  
No Donors ◽  
Receptor Agonists ◽  
Late Preconditioning ◽  
Opioid Receptor Agonist

Although ischemia-induced late preconditioning (PC) is known to be mediated by inducible nitric oxide (NO) synthase (iNOS), the role of this enzyme in pharmacologically induced late PC remains unclear. We tested whether targeted disruption of the iNOS gene abrogates late PC elicited by three structurally different NO donors [diethylenetriamine/NO (DETA/NO), nitroglycerin (NTG), and S-nitroso- N-acetyl-penicillamine (SNAP)], an adenosine A1 receptor agonist [2-chloro- N6-cyclopentyladenosine (CCPA)], and a δ1-opioid receptor agonist (TAN-670). The mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. In iNOS knockout ( iNOS−/−) mice, infarct size was similar to wild-type (WT) controls, indicating that iNOS does not modulate infarct size in the absence of PC. Pretreatment of WT mice with DETA/NO, NTG, SNAP, TAN-670, or CCPA 24 h before coronary occlusion markedly reduced infarct size. In iNOS−/− mice, however, the late PC effect elicited by DETA/NO, NTG, SNAP, TAN-670, and CCPA was completely abrogated. Furthermore, in WT mice pretreated with TAN-670 or CCPA, the selective iNOS inhibitor 1400W also abolished the delayed PC properties of these drugs; 1400W had no effect in WT mice. These data demonstrate that iNOS plays an obligatory role in NO donor-induced, adenosine A1 receptor agonist-induced, and δ1-opioid receptor agonist-induced late PC, underscoring the critical role of this enzyme as a common mediator of cardiac adaptations to stress.

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