부산대학교 도서관

We assessed the involvement of serotonin receptors (5-HT-R) on pacemaker Ca2+ activity in gastrointestinal (GI). Small tissues of 100-300 mm diameter (cell cluster preparations) were prepared from the stomach and small intestine muscle (including the enteric neurones) of mice by enzymatic and mechanical treatments. After 2 to 4 days of culture, the fluo-3 AM (acetoxymethly ester of Fluo-3) was loaded to measure the intracellular Ca 2+ concentration ([Ca2+]i). In the presence of nifedipine, we measured ([Ca2+]i) oscillations in c-Kit-immunopositive pacemaker cells (= interstitial cells of Cajal: ICCs) and examined the effects of several drugs: LY-278584, 2-Methylserotonin maleatesalt, GR113808, Fluoxeline, SK&F96365, etc. RT-PCR and immunohistochemical examinations were carried out to characterize expression of serotonin receptor subtype in pacemaker cells. We conclude that endogenous 5-HT plays a crucial role in generating and maintaining pacemaker Ca2+ activity in ICCs via type 3 serotonin receptors (5-HT3) under basal conditions, and a potentiates Ca2+ responses to electrical stimuli by facilitating cholinergic neurons. Our results may provide a new therapeutic target in diseases associated with abnormal GI motility, and add an important member (i.e. ICCs) to assess the brain-gut (The Second Brain) interaction. [J Physiol Sci. 2006;56 Suppl:S148]