Relationship of EP(1-4) prostaglandin receptors with rat hypothalamic cell groups involved in lipopolysaccharide fever responses
| Autor: | T, Oka, K, Oka, T E, Scammell, C, Lee, J F, Kelly, F, Nantel, J K, Elmquist, C B, Saper |
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| Rok vydání: | 2000 |
| Předmět: |
Lipopolysaccharides
Male Neurons Fever Hypothalamus Cell Count Receptors Prostaglandin E EP2 Subtype Preoptic Area Receptors Prostaglandin E EP1 Subtype Dinoprostone Rats Rats Sprague-Dawley Receptors Prostaglandin E EP3 Subtype Animals Receptors Prostaglandin E RNA Messenger Proto-Oncogene Proteins c-fos Receptors Prostaglandin E EP4 Subtype Paraventricular Hypothalamic Nucleus |
| Zdroj: | The Journal of comparative neurology. 428(1) |
| ISSN: | 0021-9967 |
| Popis: | The action of prostaglandin E(2) (PGE(2)) in the preoptic area is thought to play an important role in producing fever. Pharmacologic evidence suggests that, among the four subtypes of E-series prostaglandin (EP) receptors, i.e., EP(1), EP(2), EP(3), and EP(4), the EP(1) receptor mediates fever responses. In contrast, evidence from mice with EP receptor gene deletions indicates that the EP(3) receptor is required for the initial (1 hour) fever after intravenous (i.v.) lipopolysaccharide (LPS). To investigate which subtypes of EP receptors mediate systemic infection-induced fever, we assessed the coexpression of Fos-like immunoreactivity (Fos-IR) and EP(1-4) receptor mRNA in nuclei in the rat hypothalamus that have been shown to be involved in fever responses. Two hours after the administration of i.v. LPS (5 microg/kg), Fos-IR was observed in the ventromedial preoptic nucleus, the median preoptic nucleus, and the paraventricular hypothalamic nucleus. In these nuclei, EP(4) receptor mRNA was strongly expressed and the Fos-IR intensely colocalized with EP(4) receptor mRNA. Strong EP(3) receptor mRNA expression was only seen within the median preoptic nucleus but Fos-IR showed little coexpression with EP(3) receptor mRNA. EP(2) receptor mRNA was not seen in the PGE(2) sensitive parts of the preoptic area. Although approximately half of the Fos-immunoreactive neurons also expressed EP(1) receptor mRNA, EP(1) mRNA expression was weak and its distribution was so diffuse in the preoptic area that it did not represent a specific relationship. In the paraventricular nucleus, EP(4) mRNA was found in most Fos-immunoreactive neurons and levels of EP(4) receptor expression increased after i.v. LPS. Our findings indicate that neurons expressing EP(4) receptor are activated during LPS-induced fever and suggest the involvement of EP(4) receptors in the production of fever. |
| Databáze: | OpenAIRE |
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