keyword
MENU ▼
Read by QxMD icon Read
search

Non-opioid bradykinin

keyword
https://www.readbyqxmd.com/read/27756562/cyclic-non-opioid-dynorphin-a-analogues-for-the-bradykinin-receptors
#1
Yeon Sun Lee, Michael Remesic, Cyf Ramos-Colon, Sara M Hall, Alexander Kuzmin, David Rankin, Frank Porreca, Josephine Lai, Victor J Hruby
Nerve injury and inflammation cause up-regulation of an endogenous opioid ligand, dynorphin A (Dyn A), in the spinal cord resulting in hyperalgesia via the interaction with bradykinin receptors (BRs). This is a non-opioid neuroexcitatory effect that cannot be blocked by opioid antagonists. Our systematic structure-activity relationships study on Dyn A identified lead ligands 1 and 4, along with the key structural feature (i.e. amphipathicity) for the BRs. However, the ligands showed very low metabolic stability in plasma (t1/2 <1h) and therefore, in order to improve their metabolic stabilities with retained biological activities, various modifications were performed...
October 6, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27660244/constitutive-desensitization-of-opioid-receptors-in-peripheral-sensory-neurons
#2
Laura C Sullivan, Teresa S Chavera, Raehannah J Jamshidi, Kelly A Berg, William P Clarke
Opioid receptors expressed by peripheral pain-sensing neurons are functionally inactive for antinociceptive signaling under most basal conditions; however, tissue damage or exposure to inflammatory mediators (e.g., bradykinin) converts these receptors from a nonresponsive state to a functionally competent state. Here we tested the hypothesis that the basal, nonresponsive state of the mu- and delta-opioid receptors (MOR and DOR, respectively) is the result of constitutive receptor activity that activates desensitization mechanisms, resulting in MOR and DOR receptor systems that are constitutively desensitized...
December 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27619237/discovery-of-stable-non-opioid-dynorphin-a-analogues-interacting-at-the-bradykinin-receptors-for-the-treatment-of-neuropathic-pain
#3
Sara M Hall, Lindsay LeBaron, Cyf Ramos-Colon, Chaoling Qu, Jennifer Yanhua Xie, Frank Porreca, Josephine Lai, Yeon Sun Lee, Victor J Hruby
Dynorphin A (Dyn A) is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors with a preference for the kappa receptor but also neuroexcitatory effects, which cause hyperalgesia. We have shown that the neuroexcitatory effects are mediated through bradykinin (BK) receptors and that intrathecal (i.th.) administration of our lead ligand 1, [des-Arg(7)]-Dyn A-(4-11), which shows good binding affinity (IC50 = 150 nM) at the BK receptors, blocks Dyn A-induced hyperalgesia in naïve animals and reverses thermal and tactile hypersensitivities in a dose-dependent manner in nerve-injured animals...
September 27, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27568556/grk2-constitutively-governs-peripheral-delta-opioid-receptor-activity
#4
Allison Doyle Brackley, Ruben Gomez, Armen N Akopian, Michael A Henry, Nathaniel A Jeske
Opioids remain the standard for analgesic care; however, adverse effects of systemic treatments contraindicate long-term administration. While most clinical opioids target mu opioid receptors (MOR), those that target the delta class (DOR) also demonstrate analgesic efficacy. Furthermore, peripherally restrictive opioids represent an attractive direction for analgesia. However, opioid receptors including DOR are analgesically incompetent in the absence of inflammation. Here, we report that G protein-coupled receptor kinase 2 (GRK2) naively associates with plasma membrane DOR in peripheral sensory neurons to inhibit analgesic agonist efficacy...
September 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/26221618/blockade-of-non-opioid-excitatory-effects-of-spinal-dynorphin-a-at-bradykinin-receptors
#5
Yeon Sun Lee, Sara M Hall, Cyf Ramos-Colon, Michael Remesic, David Rankin, Todd W Vanderah, Frank Porreca, Josephine Lai, Victor J Hruby
Dynorphin A (Dyn A) is an endogenous opioid ligand that possesses neuroinhibitory (antinociceptive) effects via μ, δ, and κ opioid receptors. However, under chronic pain conditions, up-regulated spinal Dyn A can also interact with bradykinin receptors (BRs) to promote hyperalgesia through a neuroexcitatory(pronociceptive) effect. These excitatory effects cannot be blocked by an opioid antagonist, and thus are non-opioid in nature. On the basis of the structural dissimilarity between Dyn A and endogenous BR ligands, bradykinin(BK) and kallidin (KD), Dyn A's interaction with BRs could not be predicted, and provided an opportunity to identify a novel potential neuroexcitatory target...
2015: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/25434001/modification-of-amphipathic-non-opioid-dynorphin-a-analogues-for-rat-brain-bradykinin-receptors
#6
Yeon Sun Lee, Sara M Hall, Cyf Ramos-Colon, Michael Remesic, Lindsay LeBaron, Ann Nguyen, David Rankin, Frank Porreca, Josephine Lai, Victor J Hruby
It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A's interaction with the BRs in the central nervous system. In our earlier structure-activity relationship (SAR) study, [des-Arg(7)]-Dyn A-(4-11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using naïve or injured animals...
January 1, 2015: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/25282551/structure-activity-relationships-of-non-opioid-des-arg-7-dynorphin-a-analogues-for-bradykinin-receptors
#7
Yeon Sun Lee, David Rankin, Sara M Hall, Cyf Ramos-Colon, Jose Juan Ortiz, Robert Kupp, Frank Porreca, Josephine Lai, Victor J Hruby
In our earlier studies, bradykinin receptors (BRs) were identified as a potential target for the neuroexcitatory effects of dynorphin A (Dyn A) in the central nervous system (CNS), and [des-Arg(7)]-Dyn A-(4-11) (6) was discovered as a lead ligand to modulate Dyn A-(2-13) induced neuroexcitatory effects in the CNS as an antagonist. In an effort to gain insights into key structural features of the Dyn A for the BRs, we pursued further structure-activity relationships (SAR) study on the [des-Arg(7)]-Dyn A analogs and confirmed that all of the [des-Arg(7)]-Dyn A analogues showed good binding affinities at the BRs...
November 1, 2014: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/24937046/neuropathic-plasticity-in-the-opioid-and-non-opioid-actions-of-dynorphin-a-fragments-and-their-interactions-with-bradykinin-b2-receptors-on-neuronal-activity-in-the-rat-spinal-cord
#8
Kirsty Bannister, Yeon Sun Lee, Leonor Goncalves, Frank Porreca, Josephine Lai, Anthony H Dickenson
Dynorphin A is an endogenous opioid peptide derived from the precursor prodynorphin. The proteolytic fragment dynorphin A (1-17) exhibits inhibitory effects via opioid receptors. Paradoxically, the activity of the dynorphin system increases with chronic pain and neuropathy is associated with the up-regulation of dynorphin biosynthesis. Dynorphin A (1-17) is cleaved in vivo to produce a non-opioid fragment, dynorphin A (2-17). Previously, a mechanism by which the non-opioid fragment promotes pain through agonist action at bradykinin receptors was revealed...
October 2014: Neuropharmacology
https://www.readbyqxmd.com/read/24742335/discovery-of-amphipathic-dynorphin-a-analogues-to-inhibit-the-neuroexcitatory-effects-of-dynorphin-a-through-bradykinin-receptors-in-the-spinal-cord
#9
Yeon Sun Lee, Dhanasekaran Muthu, Sara M Hall, Cyf Ramos-Colon, David Rankin, Jackie Hu, Alexander J Sandweiss, Milena De Felice, Jennifer Yanhua Xie, Todd W Vanderah, Frank Porreca, Josephine Lai, Victor J Hruby
We hypothesized that under chronic pain conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) in the spinal cord to promote hyperalgesia through an excitatory effect, which is opposite to the well-known inhibitory effect of opioid receptors. Considering the structural dissimilarity between Dyn A and endogenous BR ligands, bradykinin (BK) and kallidin (KD), this interaction could not be predicted, but it allowed us to discover a potential neuroexcitatory target. Well-known BR ligands, BK, [des-Arg(10), Leu(9)]-kallidin (DALKD), and HOE140 showed different binding profiles at rat brain BRs than that previously reported...
May 7, 2014: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/24555641/antinociceptive-activity-of-methanolic-extract-of-muntingia-calabura-leaves-further-elucidation-of-the-possible-mechanisms
#10
Zainul Amiruddin Zakaria, Mohd Hijaz Mohd Sani, Manraj Singh Cheema, Arifah Abdul Kader, Teh Lay Kek, Mohd Zaki Salleh
BACKGROUND: Muntingia calabura (Elaecoparceae) is a medicinal plant traditionally used, particularly, by the Peruvian people to alleviate headache and cold, pain associated with gastric ulcers or to reduce the prostate gland swelling. Following the recent establishment of antinociceptive activity of M. calabura leaf, the present study was performed to further elucidate on the possible mechanisms of antinociception involved. METHODS: The methanol extract of M. calabura (MEMC) was prepared in the doses of 100, 250 and 500 mg/kg...
2014: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/24355361/the-kinin-b1-receptor-mediates-alloknesis-in-a-murine-model-of-inflammation
#11
Jumian Feng, Yuanzhen Chen, Jialing Xiong, Xu Chen, Jiexian Liang, Wenjin Ji
Noxious stimuli and non-noxious mechanical stimuli elicit itch (alloknesis) instead of pain on skin lesions of patients with atopic dermatitis. We previously found that bradykinin evokes an itch-related scratching response through activation of kinin B1 receptor in skin inflamed using complete Freund's adjuvant. In this study we investigated whether alloknesis is evoked in CFA-inflamed skin and the involvement of kinin receptors. In our results, alloknesis was elicited four days after CFA-inflammation. Furthermore, pretreatment with a B1 receptor antagonist or μ-opioid receptor antagonist significantly reduced alloknesis...
February 7, 2014: Neuroscience Letters
https://www.readbyqxmd.com/read/21756899/antinociceptive-and-anti-hypernociceptive-effects-of-se-phenyl-thiazolidine-4-carboselenoate-in-mice
#12
Natasha Frasson Pavin, Franciele Donato, Francielli Weber Cibin, Cristiano Ricardo Jesse, Paulo Henrique Schneider, Helena Domingues de Salles, Liliana do Amaral Soares, Diego Alves, Lucielli Savegnago
In this study, the antinociceptive, anti-hypernociceptive and toxic effects of orally administered (R)-Se-phenyl thiazolidine-4-carboselenoate (Se-PTC, 1-50 mg/kg) were evaluated in mice. Se-PTC did not change plasma aspartate (AST) and alanine aminotransferase (ALT) activities or urea and creatinine levels. Furthermore, in an open field test, Se-PTC did not alter the number of crossings and rearing. Se-PTC significantly reduced the amount of writhing when assessed by acetic acid-induced visceral nociception and attenuated the licking time of the injected paw in the early and late phases of a formalin test...
October 1, 2011: European Journal of Pharmacology
https://www.readbyqxmd.com/read/21643624/opioids-increase-bladder-cancer-cell-migration-via-bradykinin-b2-receptors
#13
Despoina Vassou, George Notas, Anastassia Hatzoglou, Elias Castanas, Marilena Kampa
Data relating opioid treatment and modification of cancer cell migration (a prerequisite of metastasis) both in vitro and in vivo are diverging. In the present report we show that opioids increase the migratory activity of bladder cancer cells (T24 and EJ) and we provide a new mechanistic insight, explaining (at least partially) their action: we report that the enhanced opioid-related cell migration is controlled (in the absence of opioid receptors) through their interaction with bradykinin B2 receptors. Indeed, in these cell lines, opioids increase migration, adhesion, spreading and invasion by re-arranging actin cytoskeleton, increasing MMP-2 and -9 secretion and triggering specific intracellular signaling cascades in a non-opioid receptor mediated manner...
September 2011: International Journal of Oncology
https://www.readbyqxmd.com/read/20376996/acute-management-of-acquired-brain-injury-part-ii-an-evidence-based-review-of-pharmacological-interventions
#14
REVIEW
Matthew J Meyer, Joseph Megyesi, Jay Meythaler, Manuel Murie-Fernandez, Jo-Anne Aubut, Norine Foley, Katherine Salter, Mark Bayley, Shawn Marshall, Robert Teasell
PRIMARY OBJECTIVE: To review the research literature on pharmacological interventions used in the acute phase of acquired brain injury (ABI) to manage ICP and improve neural recovery. MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials...
2010: Brain Injury: [BI]
https://www.readbyqxmd.com/read/19143754/antinociceptive-effect-of-a-novel-tosylpyrazole-compound-in-mice
#15
Sara M Oliveira, Camila Gewehr, Gerusa D Dalmolin, Cleber A Cechinel, Alexandre Wentz, Rogério V Lourega, Ronan C Sehnem, Nilo Zanatta, Marcos A P Martins, Maribel A Rubin, Helio G Bonacorso, Juliano Ferreira
Pain is the most common complaint in the medical field and the identification of compounds that can effectively treat painful states without induction of side-effects remains a major challenge in biomedical research. The aim of the present study was to investigate the antinociceptive effect of a novel compound, 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole (compound A) in several models of pain in mice and compare with those produced by the known trifluoromethyl-containing pyrazole compound celecoxib...
February 2009: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/18929597/further-analysis-of-the-antinociceptive-action-caused-by-p-methoxyl-diphenyl-diselenide-in-mice
#16
Cristiano R Jesse, Joao B T Rocha, Cristina W Nogueira, Lucielli Savegnago
The objective of this study was to extend our previous findings by investigating in greater detail the mechanisms that might be involved in the antinociceptive action of p-methoxyl-diphenyl diselenide, (MeOPhSe)(2), in mice. The pretreatment with nitric oxide precursor, l-arginine (600 mg/kg, intraperitoneal, i.p.), reversed antinociception caused by (MeOPhSe)(2) (10 mg/kg, p.o.) or N(G)-nitro-l-arginine (l-NOARG, 75 mg/kg, i.p.) in the glutamate test. Ondansetron (0.5 mg/kg, i.p., a 5-HT(3) receptor antagonist) and SCH23390 (0...
February 2009: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/18450375/pronociceptive-actions-of-dynorphin-via-bradykinin-receptors
#17
REVIEW
Josephine Lai, Miaw-chyi Luo, Qingmin Chen, Frank Porreca
The endogenous opioid peptide dynorphin A is distinct from other endogenous opioid peptides in having significant neuronal excitatory and neurotoxic effects that are not mediated by opioid receptors. Some of these non-opioid actions of dynorphin contribute to the development of abnormal pain resulting from a number of pathological conditions. Identifying the mechanisms and the sites of action of dynorphin is essential for understanding the pathophysiology of dynorphin and for exploring novel therapeutic targets for pain...
June 6, 2008: Neuroscience Letters
https://www.readbyqxmd.com/read/17905751/cardioprotection-by-remote-ischaemic-preconditioning
#18
REVIEW
S R Walsh, T Tang, U Sadat, D P Dutka, M E Gaunt
Perioperative myocardial infarction is a leading cause of morbidity and mortality after major non-cardiac surgery. Pharmacological agents such as beta-blockers may reduce the risk but are associated with side-effects and may be contra-indicated in some patients. Basic scientific experiments and preliminary clinical trials in humans suggest that remote ischaemic preconditioning (RIPC), where brief ischaemia in one tissue confers resistance to subsequent sustained ischaemic insults in another tissue, may provide a simple, cost-effective means of reducing the risk of perioperative myocardial ischaemia...
November 2007: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/17115041/dynorphin-a-activates-bradykinin-receptors-to-maintain-neuropathic-pain
#19
Josephine Lai, Miaw-Chyi Luo, Qingmin Chen, Shouwu Ma, Luis R Gardell, Michael H Ossipov, Frank Porreca
Dynorphin A is an endogenous opioid peptide that produces non-opioid receptor-mediated neural excitation. Here we demonstrate that dynorphin induces calcium influx via voltage-sensitive calcium channels in sensory neurons by activating bradykinin receptors. This action of dynorphin at bradykinin receptors is distinct from the primary signaling pathway activated by bradykinin and underlies the hyperalgesia produced by pharmacological administration of dynorphin by the spinal route in rats and mice. Blockade of spinal B1 or B2 receptor also reverses persistent neuropathic pain but only when there is sustained elevation of endogenous spinal dynorphin, which is required for maintenance of neuropathic pain...
December 2006: Nature Neuroscience
https://www.readbyqxmd.com/read/16650579/analgesic-activity-of-a-non-peptide-imidazolidinedione-somatostatin-agonist-in-vitro-and-in-vivo-studies-in-rat
#20
COMPARATIVE STUDY
G C Ji, S T Zhou, G Shapiro, J C Reubi, Simona Jurczyk, S M Carlton
Several lines of evidence support an important role for somatostatin receptors (SSTRs) in pain modulation. The therapeutic use of established SSTR peptide agonists for this indication is limited by their broad range of effects, need for intrathecal delivery, and short half-life. Therefore, the goal of the present study was to investigate the analgesic effect of SCR007, a new, highly selective SSTR2 non-peptide agonist. Behavioral studies demonstrated that paw withdrawal latencies to heat were significantly increased following intraplantar SCR007...
September 2006: Pain
keyword
keyword
51320
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"