The adenosine agonist NECA inhibits intestinal secretion and peristalsis.
This study aimed to determine whether the antidiarrhoeal effect of the mixed A1/A2 adenosine agonist NECA (5'-N-ethylcarboxamido adenosine) is due to inhibition of intestinal fluid transport or to contractility. Intestinal secretion was stimulated in anaesthetized rats by intra-arterial infusions of PGE2 (4 micrograms min-1) or vasoactive intestinal peptide (0.8 micrograms min-1). NECA reversed PGE2-induced secretion in the jejunum (ED50 16 micrograms kg-1) and ileum (ED50 21 micrograms kg-1, i.v.) and inhibited VIP-induced secretion in the jejunum (ED50 21.5 micrograms kg-1). NECA inhibited twitch responses (0.1 Hz, 1 ms, IC50 11.2 nM) but not tetanic contractions at 10 Hz of the transmurally stimulated guinea-pig ileum. Likewise, NECA (10 microM) 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 adenosine receptors are involved in modulating peristalsis as well as the secretory activity of the mucosa in the rat small intestine.
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Unit of Addictive Drug Research, School of Pharmaceutical Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Hancock
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D000241:Adenosine / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D003864:Depression, Chemical; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007419:Intestinal Secretions / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010528:Peristalsis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology
D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine