{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T15:32:56Z","timestamp":1698766376185},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,10,22]],"date-time":"2007-10-22T00:00:00Z","timestamp":1193011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p>The present study examines comparatively the effects of theophylline and its metabolites, 1\u2010methylxanthine (1\u2010MX), 3\u2010methylxanthine (3\u2010MX), 1,3\u2010dimethyluric acid (1,3\u2010DMU) and 1\u2010methyluric acid (1\u2010MU) along the rabbit intestine, and explores the underlying mechanism(s). In the small intestine, theophylline produces atropine\u2010 and hexamethonium\u2010sensitive increases in both the amplitude of phasic contractions and the basal tone. All metabolites mimic the theophylline's stimulating effect. In particular, concerning the phasic contractions, all metabolites are more potent than theophylline in the duodenum and jejunum, while in the ileum, only 1\u2010MU is more potent. Regarding the basal tone, the metabolites show, in most cases, higher efficacy in all small intestinal regions, the maximum effects of 3\u2010MX and 1\u2010MU on the duodenum and ileum being double or triple the one of theophylline. In the ascending colon, while lower concentrations of theophylline produce an atropine\u2010 and hexamethonium\u2010sensitive increase in the basal tone, higher ones produce a postsynaptic, nonadrenergic noncholinergic (NANC) relaxing effect. 1\u2010MU mimics, in a weaker manner, theophylline's effect, while the other metabolites produce only relaxation, the potency rank of order being 3\u2010MX&gt;1\u2010MX=1,3\u2010DMU&gt;theophylline. It is suggested that the theophylline and its metabolites stimulatory effect involves a cholinergic pathway, while the relaxing one is due to 3<jats:sup>\u2032<\/jats:sup>,5<jats:sup>\u2032<\/jats:sup>\u2010cyclic adenosine monophosphate (cAMP) elevation mediated by the theophylline and its metabolites inhibitory action on phosphodiesterases (PDEs).<\/jats:p>","DOI":"10.1111\/j.1365-2885.2007.00904.x","type":"journal-article","created":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T05:53:30Z","timestamp":1193205210000},"page":"541-549","source":"Crossref","is-referenced-by-count":4,"title":["Theophylline and its metabolites produce a stimulating cholinergic effect on the small intestine and a nonadrenergic noncholinergic relaxing effect on the colon: a comparative study in the rabbit intestine"],"prefix":"10.1111","volume":"30","author":[{"given":"T. A.","family":"PSARRA","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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