cyclic-gmp and 5-hydroxy-6-8-11-14-eicosatetraenoic-acid

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

Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone (LH) release and cyclic guanosine 3',5-cyclic monophosphate (cGMP) production in rat anterior pituitary cells through a calcium-dependent activation mechanism that involves increased phospholipid turnover and liberation of arachidonic acid. In enriched pituitary gonadotrophs, LH release was stimulated by arachidonic acid and its oxygenated metabolite, 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), in a dose-dependent manner. The prominent LH responses of purified gonadotrophs to arachidonic acid suggest that the secretory actions of arachidonate are exerted primarily on the gonadotroph and do not involve the participation of other pituitary cell types. Preincubation of pituitary cells with stimulatory concentrations of arachidonic acid for up to 120 min did not alter the subsequent LH responses elicited by GnRH, indicating that the secretory mechanism was unimpaired by arachidonate treatment and that no cross-desensitization occurs during sequential exposure of gonadotrophs to the two stimuli of LH release. Cyclic adenosine 3',5-monophosphate (cAMP) production was stimulated by 10 microM arachidonic acid to the same degree (about 2-fold) as by GnRH, but did not parallel the progressive LH response to higher arachidonate concentrations. cGMP production was initially stimulated by addition of arachidonic acid but returned to the control value after 5 min, whereas GnRH typically elicited a prolonged cGMP response. In contrast to the calcium-independent action of arachidonic acid, the stimulatory effect of 5-HETE on LH release required the presence of extracellular Ca2+, as previously observed for GnRH. These findings demonstrate that arachidonic acid and its metabolite, 5-HETE, partially reproduce the actions of GnRH upon LH release and cyclic nucleotide production.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Calcium; Cell Separation; Cells, Cultured; Cyclic AMP; Cyclic GMP; Female; Hydroxyeicosatetraenoic Acids; Indomethacin; Luteinizing Hormone; Pituitary Gland, Anterior; Pituitary Hormone-Releasing Hormones; Rats; Rats, Inbred Strains