Article

Potentiation of morphine analgesia by BQ123, an endothelin antagonist.

Department of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612-7231, USA.
Peptides (impact factor: 2.43). 11/2002; 23(10):1837-45. DOI:10.1016/S0196-9781(02)00141-9 pp.1837-45
Source: PubMed

ABSTRACT Several neurotransmitter mechanisms have been proposed to play a role in the actions of morphine. The present study is the first to provide evidence that central endothelin (ET) mechanisms are involved in the modulation of pharmacological actions of morphine. The effect of intracerebroventricular (i.c.v.) administration of endothelin-A (ET(A)) antagonist, BQ123, on morphine-induced analgesia, hyperthermia, and catalepsy was determined in the rat. Morphine produced a significant increase in tail-flick latency as compared to control group. Pretreatment with BQ123 significantly potentiated the effect and duration of morphine (2 and 8 mg/kg, s.c.)-induced analgesia as compared to vehicle-pretreated control rats. The hyperthermic effect of morphine was not only significantly greater in BQ123-pretreated rats but also lasted for more than 6 h. ET antagonist, BQ123, did not affect the pharmacological effect of morphine on cataleptic behavior. These studies demonstrate that BQ123, a specific ET(A) receptor antagonist, significantly potentiated morphine-induced analgesia and hyperthermia in rats without affecting morphine-induced cataleptic behavior. [(3)H]-Naloxone binding was carried out to determine the possibility of BQ123 acting on opiate receptors. It was found that morphine could displace [(3)H]-naloxone but BQ123 did not affect [(3)H]-naloxone binding even at 1,000 nM concentration. Therefore, it can be concluded that BQ123 does not act on opioid receptors. This is the first report suggesting that an ET(A) antagonist, BQ123, significantly potentiates the analgesic effect of morphine, possibly through a nonopioid mechanism.

0 0
 · 
0 Bookmarks
 · 
23 Views
  • Source
    Article: Einfluss des Endothelin – A – Rezeptorantagonisten Atrasentan auf das Wachstumsverhalten des Mammakarzinoms in vivo
    Volker Meyer
    [show abstract] [hide abstract]
    ABSTRACT: Die Endothelin (ET)-Achse stellt ein potentielles Ziel für die Therapie des Mammakarzinoms dar. In dieser Arbeit wird der Einfluss des selektiven ETAR-Antagonisten Atrasentan (ABT-627) auf das Wachstum von Mammakarzinom-Xenografttumoren im Mausmodell untersucht. Zunächst wurden 40 Mäuse in 4 Therapiearmen nach s.c. Injektion von Mammakarzinomzellen (MCF-7) in die rechte Flanke mit 1)Atrasentan 2)Paclitaxel 3)einer Kombination und 4) Trägerlösung behandelt. In einer zweiten Versuchsreihe wurden insgesamt 16 Mäuse entweder mit Atrasentan oder Trägerlösung behandelt. Ergebnisse: Es zeigte sich eine signifikante Wachstumshemmung der Tumore durch die Atrasentan-Therapie im Vergleich zur Kontrollgruppe (p = 0,002). In der zweiten Versuchsreihe wurde bei der Hälfte der Mäuse ein Tumorwachstum verhindert. Diskussion: Wir schlussfolgern aus unseren Daten, dass durch selektive Hemmung von ETAR mittels Atrasentan das Wachstum ETAR–positiver Tumoren in vivo gehemmt werden kann. Introduction: The Endothelin (ET)-axis represents a potential target of breast cancer therapy. In this study, the effect of the selective ETAR-antagonist Atrasentan (ABT-627) on breast cancer xenografts is investigated in a mouse model. First of all, MCF-7 breast cancer cells were implanted into the flank of mice. Afterwards, mice were distributed to 4 subgroups and treated with 1)Atrasentan 2)Paclitaxel 3)a combination and 4)resolvent. In a second series 16 mice got treated either with Atrasentan or with resolvent. Results: Compared to the control group, a significant reduction in tumor growth (p=0,002) of the Atrasentan-treated mice was observed. In the second series, in 4 of the 8 Atrasentan-treated mice, the tumor growth was inhibited. Discussion: In conclusion: Inhibition of ETAR by Atrasentan reduces tumor growth in vivo.
  • Source
    Article: Endogenous opiates and behavior: 2002.
    Richard J Bodnar, Maria M Hadjimarkou
    [show abstract] [hide abstract]
    ABSTRACT: This paper is the twenty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over a quarter-century of research. It summarizes papers published during 2002 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).
    Peptides 09/2003; 24(8):1241-302. · 2.43 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

1,000 nM concentration
 
6 h. ET antagonist
 
[(3)H]-Naloxone binding
 
analgesic effect
 
BQ123-pretreated rats
 
cataleptic behavior
 
central endothelin
 
control group
 
first report
 
morphine-induced analgesia
 
morphine-induced cataleptic behavior
 
neurotransmitter mechanisms
 
opiate receptors
 
opioid receptors
 
pharmacological actions
 
pharmacological effect
 
potentiated morphine-induced analgesia
 
Pretreatment
 
tail-flick latency
 
vehicle-pretreated control rats