Immunohistochemical localization of prostaglandin EP3 receptor in the rat nervous system

Nakamura, Kazuhiro; Kaneko, Takeshi; Yamashita, Yoko; Hasegawa, Hiroshi; Katoh, Hironori; Negishi, Manabu

doi:10.1002/(sici)1096-9861(20000612)421:4<543::aid-cne6>3.0.co;2-3

Cited by 193 publications

(190 citation statements)

References 64 publications

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…However, activation of EP 3 receptors mainly inhibits cAMP generation via Gi coupled mechanisms (Hatae et al, 2002). A large population of EP 3 receptors has been identified in the PAG (Ek et al, 2000;Nakamura et al, 2000). The present experiment provides additional evidence suggesting that EP 3 may appear at the presynaptic glutamatergic terminals in the PAG.…”

Section: Discussionsupporting

confidence: 54%

“…Whether EP 3 receptors are present on glutamatergic terminals of presynaptic sites of the dl-PAG has not, to our knowledge, been reported although EP 3 immunoreactivity has been identified in the dl-PAG (Ek et al, 2000;Nakamura et al, 2000). Our data from the current experiment demonstrated that activation of EP 3 receptors decreased glutamate release from presynaptic sites.…”

Section: Discussioncontrasting

confidence: 47%

“…Studies have further shown that PGE 2 receptors appear in several supraspinal regions including hypothalamus, midbrain periaqueductal gray (PAG) and hippocampus (Ek et al, 2000;Nakamura et al, 2000). Among the PGE 2 receptor subtypes (EP 1-4 ), EP 3 has been reported to mediate a number of the physiological functions of PGE 2 in the CNS such as pain modulation and regulation of the autonomic nervous system (Kumazawa et al, 1993;Oka et al, 1997;Yokotani et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Among the PGE 2 receptor subtypes (EP 1-4 ), EP 3 has been reported to mediate a number of the physiological functions of PGE 2 in the CNS such as pain modulation and regulation of the autonomic nervous system (Kumazawa et al, 1993;Oka et al, 1997;Yokotani et al, 1995). EP 3 receptors have specifically been localized in the PAG (Ek et al, 2000;Nakamura et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

Xing

2007

Brain Research

View full text Add to dashboard Cite

The purpose of this study was to determine the role of prostaglandin E 2 (PGE 2 ) in modulating neuronal activity of the dorsolateral periaqueductal gray (dl-PAG) through excitatory and inhibitory synaptic inputs. First, whole cell voltage-clamp recording was performed to obtain excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) of the dl-PAG neurons. Our results show that PGE 2 significantly decreased the frequency of miniature EPSCs and amplitude of evoked EPSCs. The effects were mimicked by sulprostone, an agonist to PGE 2 EP 3 receptors. In contrast, PGE 2 had no distinct effect on IPSCs. In addition, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. PGE 2 significantly attenuated the discharge rate of the dl-PAG neurons. The decreased firing activity was abolished in the presence of glutamate NMDA and non-NMDA receptors antagonists. The results from the current study provide the first evidence indicating that PGE 2 inhibits the neuronal activity of the dl-PAG via selective attenuation of glutamatergic synaptic inputs, likely due to activation of presynaptic EP 3 receptors.

show abstract

Section: Discussionsupporting

confidence: 54%

Section: Discussioncontrasting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

Xing

2007

Brain Research

View full text Add to dashboard Cite

show abstract

“…Among the 4 subtypes of EP receptors, expression in the spinal cord is best documented for the EP2 and EP3 subtypes (22)(23)(24). We therefore determined the contribution of these receptors to spinal PGE 2 -induced hyperalgesia.…”

Section: Spinal Hyperalgesic Properties Of Different Pgsmentioning

confidence: 99%

Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype

Reinold¹,

Ahmadi²,

Depner³

et al. 2005

J. Clin. Invest.

View full text Add to dashboard Cite

Blockade of prostaglandin (PG) production by COX inhibitors is the treatment of choice for inflammatory pain but is also prone to severe side effects. Identification of signaling elements downstream of COX inhibition, particularly of PG receptor subtypes responsible for pain sensitization (hyperalgesia), provides a strategy for better-tolerated analgesics. Here, we have identified PGE 2 receptors of the EP2 receptor subtype as key signaling elements in spinal inflammatory hyperalgesia. Mice deficient in EP2 receptors (EP2 -/-mice) completely lack spinal PGE 2 -evoked hyperalgesia. After a peripheral inflammatory stimulus, EP2 -/-mice exhibit only short-lasting peripheral hyperalgesia but lack a second sustained hyperalgesic phase of spinal origin. Electrophysiological recordings identify diminished synaptic inhibition of excitatory dorsal horn neurons as the dominant source of EP2 receptor-dependent hyperalgesia. Our results thus demonstrate that inflammatory hyperalgesia can be treated by targeting of a single PG receptor subtype and provide a rational basis for new analgesic strategies going beyond COX inhibition.

show abstract

Agents Acting on Prostanoid Receptors

Jenkins

Humphrey

Coleman³

2003

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

The prostaglandins and thromboxanes comprise a family of C 20 fatty acids, known as the prostanoids. They are primarily synthesized from arachidonic acid and exert a multitude of physiological and pathophysiological actions through the activation of membrane‐bound receptors. The current scheme of prostanoid receptor classification proposes receptors for each of the naturally occurring prostanoids and was originally based on comparisons of prostanoid receptor agonist and antagonist potencies in functional preparations. This scheme has been confirmed and expanded by the use of molecular techniques, which have led to the cloning of the known prostanoid receptors and also the discovery of a number of prostanoid receptor subtypes and isoforms. Many compounds with varying potencies and selectivities at the known prostanoid receptors have been synthesized, although few have proved highly valuable in the clinic. The use of prostanoids in clinical practice has been largely limited to those occurring naturally, where they are used predominantly as abortifacients and in the induction of labor. Several synthetic analogs have also been used for these and other purposes, including the treatment of gastric ulcers and glaucoma. Hopefully, the next few years will lead to the further discovery of new prostanoid receptor ligands that will become successful medicines.

show abstract

Immunohistochemical localization of prostaglandin EP3 receptor in the rat nervous system

Cited by 193 publications

References 64 publications

Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype

Agents Acting on Prostanoid Receptors

Contact Info

Product

Resources

About