Nitric oxide selectively inhibits adenylyl cyclase isoforms 5 and 6

Cell Signal. 2000 Apr;12(4):233-7. doi: 10.1016/s0898-6568(99)00082-0.


We have previously shown that N18TG2 neuroblastoma cells express the type 6 adenylyl cyclase and that preincubation with nitric oxide (NO) attenuates Gs- and forskolin-stimulated activity. Here we show that this inhibition reflects a direct action of NO on the adenylyl cyclase. Preincubation of N18TG2 cell membranes and insect cell membranes expressing recombinant type 5 and type 6 isoforms with NO donors leads to an inhibition of forskolin-stimulated adenylyl cyclase activity. NO donors do not alter the type 1 (representative of the type 1,3,8 family) or type 2 (representative of the type 2,4, 7 family) isoforms expressed in insect cells, even under conditions of compromised assay conditions or a range of temperatures. Thus, the ability of NO to inhibit adenylyl cyclase stimulation is dependent upon the nature of the isoform present, and appears to represent a unique regulation of the type 5,6 isoform family.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclase Inhibitors*
  • Animals
  • Cell Membrane / enzymology
  • Colforsin / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Neuroblastoma
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Donors / pharmacology*
  • Nitroprusside / pharmacology
  • Penicillamine / analogs & derivatives*
  • Penicillamine / pharmacology
  • S-Nitroso-N-Acetylpenicillamine
  • Tumor Cells, Cultured


  • Adenylyl Cyclase Inhibitors
  • Isoenzymes
  • Nitric Oxide Donors
  • Nitroprusside
  • Colforsin
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Penicillamine