The
adenosine derivative, 2'3'-di-O-nitro-(5'-N-ethylcarboxamido)adenosine (
DINECA), caused relaxation in several isolated smooth muscle preparations including guinea pig taenia caeci, beef coronary arteries, and rabbit small intestine. In rabbit small intestine the response profile of
DINECA action differed from that of established
adenosine receptor agonists and, in contrast with the latter, its relaxant effect was only partially reversed by the antagonist 8-p-sulfophenyltheophylline. Concentration-response curves to 5'-(N-ethylcarboxamido)adenosine (
NECA), but not those to
DINECA, were significantly shifted to the right by 100 microM of
8-sulfophenyltheophylline. Tissues exposed previously to
DINECA became refractory to
adenosine, an effect not observed with tissues exposed to
NECA, suggesting that
DINECA became bound to
adenosine receptors.
Adenylate cyclase from
neuroblastoma cells, containing Ra-type
adenosine receptors, was stimulated by
2-chloroadenosine and
NECA but not by
DINECA. The results suggest that most of the smooth muscle relaxant actions of
DINECA are not due to interaction with
adenosine receptors but are probably due to its function as a
nitrate. However,
DINECA appears to interact with
adenosine receptors, causing long lasting inhibition of
adenosine action in rabbit intestine. Such actions may contribute to the overall response to
DINECA application in vivo, although lowering of blood pressure due to the high reactivity of the vasculature to
nitrates may be the initial and major effect.