These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Lafutidine increases hepatic blood flow via potentiating the action of central thyrotropin-releasing hormone in rats.
    Author: Yoneda M, Kurosawa M, Watanobe H, Terano A.
    Journal: J Gastroenterol Hepatol; 2003 Feb; 18(2):177-84. PubMed ID: 12542603.
    Abstract:
    BACKGROUND: Lafutidine, (+/-)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyridyl]oxy-(Z)-2 butenyl]acetamide, is a newly synthesized histamine H2 receptor antagonist and possesses a cytoprotective efficacy, which comprises mucin biosynthesis and stimulation of gastric blood flow mediated through capsaicin-sensitive sensory neurons and endogenous calcitonin gene-related peptide (CGRP). In the present study, an effect of lafutidine on hepatic blood flow was investigated in rats that received an intracisternal injection of a subthreshold dose of thyrotropin-releasing hormone (TRH) analog, RX 77368. METHODS: Change in hepatic blood flow was determined by laser Doppler flowmetry. Male Wistar rats were anesthetized with urethane (1.5 g/kg, i.p.), and positioned on a stereotaxic apparatus. An abdominal incision was made, and a probe of laser Doppler flowmeter was placed on the surface of the liver. After a 60-min stabilization, basal hepatic blood flow was measured for 30 min, and lafutidine (0.5, 1, 3, 5 or 10 mg/kg) or vehicle was injected into the portal vein and a subthreshold dose (1.5 ng) of RX 77368 was injected intracisternally. Hepatic blood flow was monitored for 120 min postinjection. To investigate a role of capsaicin-sensitive sensory neurons and endogenous CGRP, systemic capsaicin treatment (125 mg/kg, s.c., 10-14 days before) and intravenous infusion of a CGRP receptor antagonist, human CGRP-(8-37) (15 micro g/kg as a bolus, followed by infusion at 3 micro g/kg/h) were performed, respectively. RESULTS: Intracisternal injection of RX 77368 (1.5 ng) or intraportal lafutidine (10 mg/kg) by itself did not affect hepatic blood flow, but co-injection of intracisternal RX 77368 (1.5 ng) and intraportal lafutidine (5 mg/kg) increased it with peak response at 30 min postinjection. The effect of lafutidine on hepatic blood flow in rats given RX 77368 was dose-related over the range 1-5 mg/kg. By contrast, intracisternal injection of RX 77368 (1.5 ng) did not change hepatic blood flow in rats injected with another histamine H2 receptor antagonist, famotidine (5 mg/kg), intraportally. The stimulatory effect of co-injection of TRH analog and lafutidine was abolished by systemic capsaicin-treatment and CGRP antagonist. CONCLUSION: These data suggest that lafutidine increases hepatic blood flow by sensitizing the liver to the action of central TRH via both capsaicin-sensitive sensory neurons and endogenous CGRP in urethane-anesthetized rats.
    [Abstract] [Full Text] [Related] [New Search]