title: 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.
authors.affiliation: Merrell Dow Research Institute, Cincinnati, Ohio.
authors.forename: T H
authors.initials: TH
authors.lastname: Gieske
authors.forename: N S
authors.initials: NS
authors.lastname: Doherty
authors.forename: R
authors.initials: R
authors.lastname: Raddatz
authors.forename: D
authors.initials: D
authors.lastname: Stephens
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006168:Guinea Pigs; D006710:Homocysteine / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010276:Parasympatholytics; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D013189:SRS-A; D014372:Tubercidin / Q000494:pharmacology*
chemical_list: D010276:Parasympatholytics; D013189:SRS-A; C018258:3-deazaadenosine; D006710:Homocysteine; C065189:4',5'-didehydro-5'-deoxy-5'-fluoroadenosine; D012435:S-Adenosylhomocysteine; D000242:Cyclic AMP; D006152:Cyclic GMP; D000241:Adenosine; D014372:Tubercidin