Stimulation of fructose 1,6‐bisphosphate production in melanoma cells by α‐melanocyte‐stimulating hormone

In a 31 P‐NMR spectroscopic study of cultured M2R mouse melanoma cells, we previously demonstrated the acute stimulation of three peaks in the phosphomonoester region of the spectrum by [Ahx 4 , D Phe 7 ]α‐melanotropin (concomitant with an increase in cellular adenosine 3′,5′‐phosphate (cAMP) and a decrease in ATP [Degani, H., DeJordy, J. O. & Salomon, Y. (1991) Proc. Natl Acad. Sci. USA 88 , 1506−1510]. Chemical identification of these metabolites was performed in this study using 32 P metabolic labeling and polyethyleneimine‐cellulose thin layer chromatography in combination with 31 P‐NMR and 13 C‐NMR spectroscopic methods. Two of the stimulated signals were identified as P 1 and P 6 of fructose 1,6‐bisphosphate (Fru P 2 ) and their mode of regulation by α‐melanotropin was examined. The Fru P 2 response to α‐melanotropin coincided in time and dose with a rise in cAMP and a decrease in levels of ATP, while elevation of cAMP by forskolin alone did not increase Fru P 2 . The stimulatory effect of αmelanotropin was not associated with a change in the overall rate of glycolysis, suggesting that Fru P 2 levels were not rate limiting in this process. The data suggest the presence of a previously unknown response of M2R melanoma cells to α‐melanotropin, which coincides in time with enhanced cAMP accumulation but is not mediated by cAMP and may relate to the control of Fru P 2 in a non glycolytic context.