Thromboxane A2, released by the anti-tumour drug irinotecan, is a novel stimulator of Cl- secretion in isolated rat colon. 1997

H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.

1. A camptothecin derivative, irinotecan (Cpt-11), is a topoisomerase I inhibitor and has a strong activity against a broad range of human cancer. One of the side-effects of this drug is diarrhoea. Here, we tried to determine the mediator of the irinotecan-induced Cl- secretion which may underlie this diarrhoea, using isolated mucosae of rat distal colon. 2. Irinotecan increased Cl- secretory current in a concentration-dependent manner across the mucosa, set between Ussing chambers. Thromboxane A2 (TXA2) has not been reported to date as a physiological stimulant of Cl- secretion in the distal colon. However, the major part of the present irinotecan-induced current was inhibited by selective thromboxane A2 receptor antagonists (KW-3635 and ONO-3708), and a selective thromboxane synthase inhibitor (Y-20811). In fact, we found that irinotecan stimulated the release of TXA2 in a concentration-dependent manner from the isolated mucosa into the bathing solutions. 3. Furthermore, 9,11-epithio-11,12-methano-thromboxane A2 (STA2), a stable analogue of TXA2, induced Cl- secretion, which was almost completely inhibited by the TXA2 receptor antagonists. 4. In single cells of isolated crypts, STA2 depolarized the cell and increased the membrane conductance, indicating that STA2 opened the apical Cl- channel of the crypt cells. 5. We conclude, therefore, that the irinotecan-induced endogenous TXA2 is a novel stimulant of the Cl- secretion from the crypt cells of distal colon.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009579 Nitrobenzoates Benzoic acid or benzoic acid esters substituted with one or more nitro groups. Nitrobenzoic Acids,Acids, Nitrobenzoic
D002166 Camptothecin An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. Camptothecine
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D005260 Female Females

Related Publications

H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
August 2002, The Journal of physiology,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
February 2005, The Journal of physiology,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
October 2000, The Journal of pharmacology and experimental therapeutics,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
July 2000, European journal of pharmacology,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
January 1991, Eicosanoids,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
June 2002, British journal of pharmacology,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
March 1995, Naunyn-Schmiedeberg's archives of pharmacology,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
December 1989, Biomedical & environmental mass spectrometry,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
December 1993, Pflugers Archiv : European journal of physiology,
H Sakai, and T Sato, and N Hamada, and M Yasue, and A Ikari, and B Kakinoki, and N Takeguchi
January 1982, Prostaglandins,
Copied contents to your clipboard!