Background. Daikencyuto (DKT) is a traditional Japanese medicine (Kampo) and is a mixture of extract powders from dried Japanese pepper, processed ginger, ginseng radix and maltose powder, and has been used as the treatment of paralytic ileus. DKT may increase gastrointestinal motility by an up-regulation of the calcitonin gene-related peptide (CGRP). CGRP is also the most powerful vasoactive substance. In the present study, we investigated whether DKT has any effect on the colonic blood flow (CBF) in rats. Materials and Methods. Experiments were performed on fasted anesthetized and artificially ventilated Wistar rats. Systemic mean arterial blood pressure (MAP) and heart rate (HR) were recorded. Red blood cell flux in CBF was measured using non-contact laser tissue blood flowmetry, and colonic vascular conductance (CVC) was calculated as the ratio of flux to MAP. We examined four key physiological mechanisms underlying the response using blocker drugs: CGRP1 receptor blocker (CGRP_<8-37>), nitric oxide synthase inhibitor (L-NAME), vasoactive intestinal polypeptide (VIP) receptor blocker ([4-Cl-DPhe6, Leu17]-VIP), and substance P (SP) receptor blocker (spantide). RT-PCR was employed for the detection of mRNA of calcitonin receptor-like receptor (CRLR), receptor-activity modifying protein 1 (RAMP1), the component of CGRP 1 receptor and CGRP. After laparotomy, a cannula was inserted into the proximal colon to administer the DKT and to measure CVC at the distal colon. Results. Intracolonal administration of DKT (10, 100 and 300 mg/kg) increased CVC (basal CVC, 0.10 mL/mmHg) from the first 15-min observation period (0.14, 0.17 and 0.17 mL/mmHg , respectively) and with peak response at either 45 min (0.17 mL/mmHg by 10 mg/kg), or at 75 min and 60 min (0.23 and 0.21 mL/mmHg by 100 mg/kg and 300 mg/kg, respectively). CGRP_<8-37> completely abolished the DKT-induced hyperemia, whereas L-NAME partially attenuated the DKT-induced hyperemia. [4-Cl-DPhe6, Leu17]-VIP and spantide did not affect the hyperemia. Japanese pepper significantly increased CVC at 45 min or later, whereas ginseng radix only showed significant increase at 15 min. RT-PCR showed that mRNA for CRLR, RAMP1 and CGRP were expressed in rat colon and upregulated by DKT. Conclusions. The present study demonstrated that DKT increased CVC which was mainly mediated by CGRP and its receptor components.
