MK-801 blocks dynorphin A (1–13)-induced loss of the tail-flick reflex in the rat

Isaac, Lawrence; O'Malley, Terri Van Zandt; Ristic, Helen; Stewart, Peggy

doi:10.1016/0006-8993(90)90760-9

Cited by 36 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If endogenous dynorphin acts at K2 receptors, the question then becomes what physiological function do K2 receptors perform and how can we measure that function? Several studies have suggested that dynorphin may play a role in the regulation of NMDA receptors (Caudle and Isaac, 1988a,b;Bakshi and Faden, 1990a,b;Faden et al, 1990;Isaac et al, 1990;Shukla et al, 1992;Skilling et al, 1992). In these studies, selective antagonists to the NMDA receptor complex blocked the effects of exogenously applied dynorphin.…”

mentioning

confidence: 66%

Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells

1994

View full text Add to dashboard Cite

The role of the endogenous opioid peptide dynorphin (1–17) in regulating NMDA receptor-mediated synaptic currents was examined in guinea pig hippocampus. Schaffer collateral/commissural fiber-evoked NMDA synaptic currents were recorded using whole-cell patch-clamp techniques in CA3 pyramidal cells. Dynorphin was found to have dual effects on NMDA synaptic currents, increasing currents at low concentrations and decreasing currents at high concentrations. Only the inhibitory action of dynorphin was sensitive to naloxone, indicating that this effect was mediated by an opioid receptor. The inhibitory effect was mimicked by bremazocine, but not by U69,593, U50,488, [D- Ala2, N-Me-Phe4, Gly-ol]-enkephalin, or [D-Pen2,5]-enkephalin. Bremazocine's effect was blocked by naloxone, but not by nor- binaltorphimine, cyprodime, or naltrindole. These findings suggest that bremazocine's effect was mediated by the kappa 2 subtype of opioid receptor. In addition, 1 microM naloxone and antisera to dynorphin (1– 17) were found to increase NMDA-mediated synaptic currents. Nor- binaltorphimine, cyprodime, naltrindole, and antisera to met-enkephalin did not increase the NMDA synaptic current. These findings suggest that endogenous dynorphin was acting at kappa 2 receptors to inhibit NMDA receptor-mediated synaptic currents. Overall, these findings indicate that dynorphin is an endogenous agonist for kappa 2 receptors in the CA3 region of the guinea pig hippocampus and that these receptors regulate NMDA receptor function.

show abstract

mentioning

confidence: 66%

Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells

1994

View full text Add to dashboard Cite

show abstract

“…These studies reported a transient Dyn A-mediated analgesia up to one hour that was reversible by a KOR antagonist (60). But studies of IT des-Tyr-Dyn A showed short-term hyperalgesic responses that were not naloxone reversible (Table 2A) (62, 63). …”

Section: Spinal Intrathecal Dynorphin Pharmacology Demonstrates Amentioning

confidence: 99%

The Emerging Role of Spinal Dynorphin in Chronic Pain: A Therapeutic Perspective

Podvin

Yaksh²,

Hook

2016

Annu. Rev. Pharmacol. Toxicol.

View full text Add to dashboard Cite

Notable findings point to the significance of the dynorphin peptide neurotransmitter in chronic pain. Spinal dynorphin neuropeptide levels are elevated during development of chronic pain. Importantly, knockout of the dynorphin gene prevents development of chronic pain in mice, but acute nociception is unaffected. Intrathecal (IT) administration of opioid and non-opioid dynorphin peptides initiate allodynia through a non-opioid receptor mechanism; furthermore, anti-dynorphin antibodies administered by the IT route attenuate chronic pain. Thus, this review presents the compelling evidence in the field supporting the role of dynorphin in facilitating the development of a persistent pain state. These observations raise the question of the control mechanisms responsible for the upregulation of spinal dynorphin leading to chronic pain development. Also, spinal dynorphin regulation of downstream signaling molecules may be implicated in hyperpathic states. Therapeutic strategies to reduce spinal dynorphin may provide a non-addictive approach to improve the devastating condition of chronic pain that occurs in numerous human diseases.

show abstract

“…There is also a glycine binding domain which facilitates the opening of the ion channel, and the entry of Ca 2+ and Na + through this channel is modulated by Zn 2+ , phencyclidine, polyamines and other regulatory agents [20]. Dynorphin has been shown to both stimulate and inhibit the release of glutamate [21, 22], and there is much controversy as to whether dynorphin may interact with the glutamate site [23], glycine site [24]or the site within the ion channel [25], or alter the gating properties of these channels [26]. MK-801 is a noncompetitive antagonist that acts by occupying a site within the ion channel, although it is unlikely that dynorphin can actually enter the channel because of its molecular size.…”

Section: Discussionmentioning

confidence: 99%

The Role of N-Methyl-D-Aspartate Receptors in the Release of Adrenocorticotropin by Dynorphin A<sub>1–13</sub>

Szeto¹,

Soong²,

Wu³

1999

Neuroendocrinology

View full text Add to dashboard Cite

We previously reported that dynorphin A_1–13 evokes a significant increase in plasma adrenocorticotropin (ACTH) after intravenous administration in the ovine fetus. This response was not sensitive to naloxone and was regulated differently from the response to U50,488H, a selective ĸ-opioid agonist. NMDA appears to play a role in many of the nonopioid actions of dynorphin. We therefore hypothesized that dynorphin A_1–13 may release ACTH via N-methyl-D-aspartate (NMDA) receptors. To test this hypothesis, we have compared the ACTH response to dynorphin A_1–13 and NMDA in the chronically-instrumented ovine fetus. Our data show that both dynorphin A_1–13 (0.5 mg/kg) and NMDA (4 mg/kg) induced a significant release of immunoreactive ACTH in the late-term ovine fetus. The ACTH response to NMDA was of a smaller magnitude, but of longer duration, when compared to dynorphin A_1–13. The response to both dynorphin A_1–13 and NMDA was significantly attenuated by pretreatment with the noncompetitive NMDA antagonist, MK-801, but was not affected by antagonists of corticotropin-releasing hormone and arginine vasopressin. Finally, the ACTH response to both dynorphin A_1–13 and NMDA were inhibited by dexamethasone. The results of this study indicate a role for NMDA receptors in the action of dynorphin A_1–13, and suggest that NMDA may act directly at the level of the pituitary to release ACTH without the involvement of hypothalamic secretagogues.

show abstract

MK-801 blocks dynorphin A (1–13)-induced loss of the tail-flick reflex in the rat

Cited by 36 publications

References 18 publications

Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells

Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells

The Emerging Role of Spinal Dynorphin in Chronic Pain: A Therapeutic Perspective

The Role of N-Methyl-D-Aspartate Receptors in the Release of Adrenocorticotropin by Dynorphin A<sub>1–13</sub>

Contact Info

Product

Resources

About