Altered H1 histamine receptor signaling in Balb/3T3 cells transformed by v-K-ras and v-H-ras oncogenes.
Transformation of Balb/3T3 cells with the v-K-ras oncogene resulted in the expression of functional Ca(2+)-mobilizing receptors for histamine, whereas v-H-ras-transformed Balb/3T3 cells failed to show a similar response to histamine. Stimulation of histamine receptors in v-K-ras-transformed cells produced a dose-dependent increase in intracellular free calcium ([Ca2+]i), which was inhibited by the H1 histamine antagonist pyrilamine but unaffected by the H2 histamine receptor antagonist cimetidine. Histamine-mediated elevation of [Ca2+]i was partially inhibited by the removal of extracellular Ca2+, which indicates that the H1 histamine receptors mobilize intracellular Ca2+ and also promote Ca2+ influx. H1 histamine receptors were identified in both v-K-ras- and v-H-ras-transformed Balb/3T3 cells, but not in untransformed cells, using the specific H1 antagonist [3H]-pyrilamine. Transformation of Balb/3T3 cells with the viral ras oncogene results in a complex regulation of H1 histamine receptors. K-ras and H-ras transformation results in the expression of H1 histamine receptors; however, H1 receptor expression and Ca2+ mobilization are uncoupled in v-H-ras-transformed cells.
Blackmore
P F
PF
Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
Oakes
S G
SG
Somers
K D
KD
D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D011905:Genes, ras; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000502:physiology; D011738:Pyrilamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000502:physiology*; D015398:Signal Transduction
D011969:Receptors, Histamine H1; D015689:Oncogene Protein p21(ras); D011738:Pyrilamine; D002118:Calcium