title: Prostaglandin-dependent desensitization of human monocyte cAMP responses.
abstract: Histamine stimulated large increases of cyclic adenosine monophosphate (cAMP) in freshly isolated human blood monocytes in the presence of R02-1724, a specific cAMP phosphodiesterase inhibitor. This was mediated by H2 receptors, since it was inhibited by cimetidine but not chlorpheniramine. Stimulation was attenuated in cells aged in culture 1-2 days. Indomethacin prevented the desensitization, suggesting that a cyclooxygenase product was responsible. Desensitization was heterologous, since the adenylate cyclase responses to 5'-(N-ethylcarboxamido)adenosine (A2 receptor agonist), isoproterenol (beta-adrenoceptor agonist), and prostaglandin E2 (PGE2) also declined during culture. The loss of sensitivity to histamine was restored by incubating monocytes with PGE2 in the presence of indomethacin. The results indicate that, while PGE2 inhibits monocyte functions via cAMP, its accumulation paradoxically permits cells to escape this regulation through a heterologous desensitization of the cAMP response to itself and other agonists.
authors.affiliation: University of South Florida, College of Medicine, Department of Pharmacology and Therapeutics, Tampa 33612.
authors.forename: R G
authors.initials: RG
authors.lastname: Coffey
authors.forename: V A
authors.initials: VA
authors.lastname: Alberts
authors.forename: L L
authors.initials: LL
authors.lastname: Weakland
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000502:physiology
chemical_list: D011970:Receptors, Histamine H2; D019830:Adenosine-5'-(N-ethylcarboxamide); D006632:Histamine; D000242:Cyclic AMP; D000241:Adenosine; D015232:Dinoprostone; D007545:Isoproterenol; D007213:Indomethacin