cyclic-gmp and 3-deazaadenosine

The effects of two S-adenosylhomocysteine (SAH) hydrolase inhibitors, MDL 28,842 and 3-deazaadenosine (3-DAA), on the tissue levels of SAH, cAMP and cGMP and on the contractile responses to leukotriene D4 and histamine were compared in guinea-pig lung parenchyma. MDL 28,842 and 3-DAA (both in the presence of L-homocysteine) increased tissue levels of SAH to the same degree, indicating that both compounds had inhibited SAH hydrolase. However, only 3-DAA inhibited the contractile response of the lung parenchyma. The spasmolytic activity of 3-DAA was inhibited by co-incubation with MDL 28,842, suggesting that 3-DAA must be metabolized by SAH hydrolase, probably to 3-deazaadenosylhomocysteine, in order to exert its effect. 3-DAA did not elevate tissue levels of cAMP or cGMP. Although the mechanism by which 3-DAA exerts its spasmolytic effects is unknown, direct inhibition of methyltransferase is a plausible explanation. These data indicate that SHA levels do not regulate the contractile response of guinea-pig lung parenchyma.

Topics: Adenosine; Animals; Cyclic AMP; Cyclic GMP; Guinea Pigs; Homocysteine; In Vitro Techniques; Lung; Male; Parasympatholytics; S-Adenosylhomocysteine; SRS-A; Tubercidin