Cloning and expression of a cDNA for mouse prostaglandin E receptor EP2 subtype.

Honda, Akira; Sugimoto, Yukihiko; Namba, Tsunehisa; Watabe, Akiko; Irie, Atsushi; Negishi, Manabu; Narumiya, Shuh; Ichikawa, Atsushi

doi:10.1016/s0021-9258(18)53022-2

Cited by 358 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using EP 2 -specific primers, we amplified an EP 2 receptor fragment from the ovine fetal DA that had 90, 87, and 85% homology with the corresponding se-quences from the human, mouse, and rat EP 2 receptors, respectively (4,21,35). Using EP 4 specific primers, we also amplified an EP 4 fragment, which was virtually identical to the reported ovine EP 4 receptor sequence (GenBank accession AF035418) and had 94% homology with the corresponding sequence of the human EP 4 receptor (29).…”

Section: Competitive Displacement Of [ 3 H]pgementioning

confidence: 99%

Characterization of PGE₂receptors in fetal and newborn lamb ductus arteriosus

Bouayad

Kajino

Waleh

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Although the role of PGE2 in maintaining ductus arteriosus (DA) patency is well established, the specific PGE2 receptor subtype(s) (EP) involved have not been clearly identified. We used late gestation fetal and neonatal lambs to study developmental regulation of EP receptors. In the fetal DA, radioligand binding and RT-PCR assays virtually failed to detect EP1 but detected EP2, EP3D, and EP4 receptors in equivalent proportions. In the newborn lamb, DA total density was one-third of that found in the fetus and only EP2 was detected. Stimulation of EP2 and EP4 increased cAMP formation and was associated with DA relaxation. Though stimulation of EP3 inhibited cAMP formation, it surprisingly relaxed the fetal DA both in vitro and in vivo. This EP3-induced relaxation was specifically diminished by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide. In conclusion, PGE2 dilates the late gestation fetal DA through pathways that involve either cAMP (EP2 and EP4) or K(ATP) channels (EP3). The loss of EP3 and EP4 receptors in the newborn DA is consistent with its decreased responsiveness to PGE2.

show abstract

Section: Competitive Displacement Of [ 3 H]pgementioning

confidence: 99%

Characterization of PGE₂receptors in fetal and newborn lamb ductus arteriosus

Bouayad

Kajino

Waleh

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…EP1 is coupled to an unidentified G protein and two distinct signaling pathways that result in an increase in intracellular calcium (Watabe et al, 1993;Katoh et al, 1995). The EP2 and EP4 receptors are both coupled to the stimulatory G protein (Gs) and, when activated, induce adenylate cyclase activity, resulting in an increase in cAMP (Honda et al, 1993;Regan et al, 1994). Activation of the EP2 receptor, however, results in a cAMP response that is much greater than that of the EP4 receptor (Fujino et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Effects of UVB on E Prostanoid Receptor Expression in Murine Skin

Tober

Thomas‐Ahner

Kusewitt

et al. 2007

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Prostaglandin E2 (PGE2) upregulation in response to UV light exposure is a significant factor in the development of non-melanoma skin cancer. It is known that PGE2 signals via the E prostanoid receptors, EP1-4, but the role that each receptor plays in skin carcinogenesis is unclear. Immunohistochemical analysis of EP receptor staining in unirradiated and UVB-exposed SKH-1 mouse skin demonstrated the localization of EP1 and EP2 to the plasma membrane of differentiated epidermal keratinocytes. In contrast, the EP3 receptor localized to the basal layer of the epidermis in unirradiated skin and throughout the epidermis in UVB-exposed skin. In unirradiated skin, cytoplasmic EP4 staining was seen throughout the epidermis, in dermal leukocytes, and in vascular endothelium. However, UVB exposure resulted in relocalization of the EP4 receptor to the plasma membrane of keratinocytes, with no change in the dermal staining pattern. In tumors isolated from UVB-exposed mice, EP1 and EP2 staining was detected in the more differentiated cells surrounding keratin pearls, whereas EP3 and EP4 were detectable throughout the tumors. Differential expression of the EP receptors suggests that each receptor may play a distinct role in skin tumor development.

show abstract

“…The EP1-4 subtypes have been classified based on their distinct genes and signal transduction pathways. EP1 is coupled to intracellular Ca 2+ mobilization 13 , EP2 and EP4 increase intracellular cAMP concentration 14,15 , and EP3, which is reported to have three isoforms, EP3α, β, and γ, mainly inhibits intracellular cAMP accumulation 16 . It is conceivable that this diversity in signal transduction through receptors is one reason why the effects of PGE 2 are not well understood.…”

Section: Introductionmentioning

confidence: 99%