5-hydroxy-6-8-11-14-eicosatetraenoic-acid and Diarrhea

The physiology of intestinal electrolyte transport is currently an area of intense research interest. Also, reports regularly appear that define possible roles of various endocrine, paracrine, and neurohumoral substances in regulating intestinal ion and water flux. A vast body of knowledge has appeared recently that focuses on the action of specific intracellular mediators or second messengers and certain biochemical events that are thought to be involved in this transport process. This area of research has drawn the attention of the clinical investigator as well as the basic scientist because of the implications of these findings to the understanding of secretory disorders of the gastrointestinal tract, in particular diarrheal disease. The purpose of this review is to focus on recent findings reported in three major areas: the physiology of intestinal electrolyte transport and its regulation; the pathophysiology of secretory diarrhea; and current thoughts and practices in the therapeutic approach to the disease.

Topics: Acid-Base Equilibrium; Adrenergic alpha-Agonists; Animals; Arachidonic Acids; Carbachol; Chlorides; Cholera Toxin; Cyclic AMP; Cyclic GMP; Diarrhea; Electric Stimulation; Electrolytes; Hydroxyeicosatetraenoic Acids; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Leukotrienes; Models, Biological; Narcotics; Phenothiazines; Phorbol 12,13-Dibutyrate; Phorbol Esters; Phosphorylation; Protein Kinase C; Receptors, Cholinergic; Receptors, Muscarinic; Renin-Angiotensin System; Sodium; Sodium-Potassium-Exchanging ATPase; Tetradecanoylphorbol Acetate

Both 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and 5-hydroxyeicosatetraenoic acid (5-HETE) increased the short-circuit current (Isc) in rabbit colonic mucosa mounted in vitro in Ussing chambers. Measurements of chlorine-36 fluxes indicated that the Isc response to 5-HPETE is due to stimulation of active chlorine secretion. 9-, 11-, and 12-HPETE's and leukotrienes C4 and B4 produced either very small increases in Isc or no increase. In contrast to results in rabbit colon, no HPETE, HETE, or leukotriene was effective in rabbit ileal mucosa. The effects of 5-HPETE in the rabbit colon were unaffected by mepacrine, but could be partially blocked by indomethacin. These results suggest that drugs which block both cyclooxygenase and lipoxygenase may be effective antidiarrheals in patients with colitis.

Topics: Animals; Arachidonic Acids; Bicarbonates; Chlorides; Colitis; Colon; Diarrhea; Hydroxyeicosatetraenoic Acids; Ileum; Indomethacin; Leukotrienes; Lipoxygenase Inhibitors; Rabbits