Effects of norepinephrine or prostaglandin E2 on extracellular acidification rate of MCG 101, or K1735-M2 tumor cells.
We studied by microphysiometry functional effects of two different signalling molecules in the murine tumor cell lines, MCG 101 and K1735-M2, namely norepinephrine (NE) and prostaglandin E2 (PGE2). This methodology implies estimation of intracellular metabolism by measurements of extracellular acidification rate (ECAR). MCG 101 (an undifferentiated, epithelial-like tumor), in contrast to K1735-M2 (a melanoma), has been found to produce great amounts of PGE2. Challenge of MCG 101 cells with PGE2 (0.284 and 2.84 microM for 9 min) elicited an increase in ECAR by about 10 and 41% above basal level, respectively. Pretreatment with indomethacin (0.5 microM) reduced the response to the two PGE2 concentrations by about 70 and 25%, respectively. In contrast, PGE2 caused virtually no response in K1735-M2 cells. Moreover, NE caused increases in ECAR in both cell types, possibly via beta3-adrenoceptors, as investigated pharmacologically in MCG 101, and by immunocytochemistry in both cell lines. The results obtained strongly suggest functional receptors for PGE2 in MCG 101, but not K1735-M2 tumor cells. Functional receptors for NE were demonstrated in both cell lines. There is possibly an autocrine loop in the MCG 101 cells, in which PGE2 activates cyclooxygenase.
Department of Surgery, Institute of Surgical Sciences, Sahlgrenska University Hospital, S 413 45 Goteborg, Sweden.
Gunnar
G
Nylund
Marianne
M
Andersson
Börje
B
Haraldsson
Dick S
DS
Delbro
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors; D014407:Tumor Cells, Cultured
D011941:Receptors, Adrenergic; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin