Substance P and astrocytes: stimulation of the cyclooxygenase pathway of arachidonic acid metabolism.
Substance P (SP) may play an important role in the interactions between the nervous system and the immune system. Astrocytes carry receptors for SP on their surfaces. We examined whether ligand-induced receptor activation would lead to the release of arachidonic acid metabolites. SP (10(-10)-10(-8) M) evokes the formation of prostaglandin E and thromboxane B2 in a dose-dependent manner. Structure-activity studies disclosed that the COOH-terminal peptide sequence of SP is primarily responsible for this biological activity. The generation by astrocytes of arachidonate-derived proinflammatory and immunoregulatory compounds in response to SP receptor activation may be relevant to immunoinflammatory responses within the central nervous system and emphasizes the concept of neuroimmunomodulation.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*
D001095:Arachidonic Acids; D011453:Prostaglandins; D013373:Substance P; D011451:Prostaglandin-Endoperoxide Synthases