Enkephalin inhibition of adenylate cyclase activity in neuroblastoma N18TG2 cells: effect of sulfatide incorporation.
Potentiation of the morphine inhibition of adenylate cyclase activity in the neuroblastoma N18TG2 cell line after sulfatide incorporation has been observed previously and a similar sulfatide effect on enkephalin inhibition was investigated. Conditions for the sulfatide incorporation were defined. Though N18TG2 cells possess a high affinity for 3H-D-Ala2-Met5 enkephalinamide (14 nM), the met5-enkephalin was relatively inactive in inhibiting the intracellular cAMP level. The IC50 value for met5-enkephalin to inhibit the prostaglandin E1 (PGE1) stimulated cAMP product was 65 nM in N18TG2 as compared to the IC50 value of 3 nM in the neuroblastoma x glioma NG108-15 hybrid. Upon exposure of the N18TG2 cells to 22 microM of sulfatide in the growth medium for 6 hours, both the potency and efficacy of the met5-enkephalin in sulfatide treated cells were found to be 3.4 nM. The degree of potentiation was dependent on the quantity  of CS added to the growth medium and the age of the culture. Furthermore, the sulfatide effect appeared to be at the adenylate cyclase complex. Basal and PGE1-stimulated adenylate cyclase activity in the cellular membrane was similarly affected by enkephalin after sulfatide incorporation. There was a lipid specificity, since in the group of lipids tested only CS and PC exhibited the potentiation effect.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D008566:Membranes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology*; D051381:Rats; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D013997:Time Factors
D000067956:Adenylyl Cyclase Inhibitors; D004723:Endorphins; D004745:Enkephalins; D009363:Neoplasm Proteins; D013433:Sulfoglycosphingolipids; D000242:Cyclic AMP