S-Adenosylhomocysteine Levels Are Not Involved in the Spasmolytic Activity of 3-Deazaadenosine in Guinea-Pig Lung Parenchyma

Abstract

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.

Morphological modifications of apoptosis in HL-60 cells: effects of homocysteine and cytochalasins on apoptosis initiated by 3-deazaadenosine

“…Addition of Hcy favours formation of c~AdoHcy [12,13,50,61]. A role for c3AdoHcy in inhibition of the contractile response in guinea-pig lung parenchyma has been shown previously by Gieske et al [21]. A role for c3AdoHcy in inhibition of the contractile response in guinea-pig lung parenchyma has been shown previously by Gieske et al [21].…”