The effect of caffeine, theophylline and adenosine on colonic transit time of guinea pig in vitro

Abstract

[한글]

[영문]

Objective : Reports on the effect of coffee on gastrointestinal tract show that coffee stimulates colonic motor activity. Both in vivo and in vitro studies show theophylline relaxes colon and taenia coli of human and several animal species. There are two important mechanisms of action by which caffeine and theophylline affect the motility of smooth muscle. The one is a non-specific PDE inhibition which reduces breakdown of cAMP and cGMP, The other is antagonism of adenosine receptor as competitive manner. This study investigated the effect of caffeine, theopylline and adenosine on colonic transit of guinea pig.Material and methods : The colon of male guinea pig (approximately 10 cm from the anus) was isolated. The each ends were connected to a chamber containing Krebs-Henseleit (K-H) solution. Artificial feces (12 mm × 4 mm) was inserted into the oral side of lumen, Total 8cm length except the first 2 cm of the segment was measured in the isolated colon and a mean transit time of four sections was calculated. Transit time was measured in the presence of caffeine, theophylline (10-8 ~ 10-6 M), adenosine (10-6 ~10-3 M) and their co-administration.Results : Caffeine (n=13) and theophylline (n=23) significantly delayed colonic transit time with dose dependent manner. Adenosine also significantly delayed colonic transit time with dose dependant pattern at higher concentration (10-4, 10-3 M) (n=13). Adenosine-induced increase in colon transit time was significantly shortened by co-treatment of 10-6 M caffeine when compared to adenosine alone at 10-3 M adenosine (1053.8±244.4% vs 646.1±159.1%, p=0.092, n=16), but 10-6 M theophylline had no effect on adenosine (n=14). When 10-8 M caffeine (429.1±137.8% vs 245.6±84.2%, p=0.043, n=5) and 10-8 M theophylline (303.4±90.2% vs 171.0±53.8%, p=0.043, n=5), respectively was administered with 10-4 M adenosine, the colonic transit time was significantly shortened when compared to 10-4 M adenosine alone.Conclusion : Caffeine, theophylline or adenosine delay colonic transit. The colonic transit time is the result of the various delay and the inhibition of delay in the various concentration of caffeine, theophylline and adenosine. The delaying effect of caffeine and theophylline on the colonic transit time is mainly due to PDE inhibition rather than adenosine antagonism.