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.
Nylund
Gunnar
G
Department of Surgery, Institute of Surgical Sciences, Sahlgrenska University Hospital, S 413 45 Goteborg, Sweden.
Andersson
Marianne
M
Haraldsson
Börje
B
Delbro
Dick S
DS
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