THE ADENOSINE AGONIST NECA INHIBITS INTESTINAL SECRETION AND PERISTALSIS

This study aimed to determine whether the antidiarrhoeal effect of the mixed A(1)/A(2) adenosine agonist NECA (5'-N-ethylcarboxamido adenosi ne) is due to inhibition of intestinal fluid transport or to contracti lity. Intestinal secretion was stimulated in anaesthetized rats by int ra-arterial infusions of PGE(2) (4 mu g min(-1)) or vasoactive intesti nal peptide (0.8 mu g min(-1)). NECA reversed PGE(2)-induced secretion in the jejunum (ED50 16 mu g kg(-1)) and ileum (ED50 21 mu g kg(-1), i.v.) and inhibited VIP-induced secretion in the jejunum (ED50 21.5 mu g kg(-1)). NECA inhibited twitch responses (0.1 Hz, 1 ms, IC50 11.2nM ) but not tetanic contractions at 10 Hz of the transmurally stimulated guinea-pig ileum. Likewise, NECA (10 mu M) did not inhibit frequency- related contractions over the range of 2.5 to 40 Hz of rat jejunum or ileum. However, NECA was shown to be a potent inhibitor (30 nM) of the peristaltic reflex in the rat ileum. The results indicate that adenos ine receptors are involved in modulating peristalsis as well as the se cretory activity of the mucosa in the rat small intestine.