Effects of platelet-activating factor on ion transport in isolated rat jejunum

Abstract

In isolated normal rat jejunum, platelet-activating factor (PAF) induced a dose-dependent increase in short-circuit current (Isc) that was reduced in chloride-free buffer and inhibited by the Cl- channel blocker, diphenylamine-2-carboxylate. An immediate rise in Isc (early phase) occurred that fell to a new elevated base line by 15 min (late phase). These responses to PAF occurred only when experiments were conducted at or before approximately 9 A.M. Early phase responses were blocked by the specific PAF antagonists, BN52021 and WEB2086, and were inhibited by the neurotoxin, tetrodotoxin. Early and late phases were also reduced by cyclooxygenase inhibitors and by doxantrazole, a mast cell stabilizing drug. However, histamine and serotonin antagonists were ineffective. We conclude that PAF causes changes in ion transport that include Cl- secretion and acts on the epithelium possibly via an intermediate cell and enteric nerves. In addition, known PAF receptors are involved in one component of the response that appears to follow a circadian rhythm.

Immune system control of rat and rabbit colonic electrolyte transport. Role of prostaglandins and enteric nervous system.

“…This is considerably greater than that necessary to stimulate chemotaxis and degranulation of phagocytes (0.01-100 nM) (20). A distinct circadian response was noted with PAF as has been noted by others in studies of rat small intestine (21). Animals studied in the afternoon had blunted or absent Isc responses and were not included in the data reported here.…”

Role of platelet activating factor in the intestinal epithelial secretory and Chinese hamster ovary cell cytoskeletal responses to cholera toxin.

“…Error bars represent 1 SD. (18)(19)(20)(21). Although other submucosal cell types may also produce PAF, as has been suggested by Berschneider and Powell (29,30), our finding that T-84 cells can directly respond to cholera toxin with increased PAF production documents that human epithelial cells may serve as an autocrine source of PAF in response to cholera toxin.…”

“…9655 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 10-5 M) and the cyclooxygenase inhibitor indomethacin (10-5 M) all significantly decreased cholera toxin-induced secretion, by 47%, 84%, and 40%6 respectively (P < 0.01 for each). Even in loops adjacent to the PAF antagonist SR 27417, 76% of the secretory response to cholera toxin was inhibited.…”

“…Because platelet activating factor (PAP), recently identified as a secretagogue (18)(19)(20)(21), can also stimulate phospholipase A2 (22,23), thereby increasing the synthesis of prostaglandins, we sought to explore the potential role of PAF in the secretory and CHO cell responses to cholera toxin. 1% fetal bovine serum and studied as described previously (7).…”

Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis. Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation.

“…Glucose (10 mM) was included in the serosal buffer and mannitol (10 mM) in the mucosal buffer. When chloride-free buffer was used, isethionate and acetate ions were substituted for chloride (36). Agar-salt bridges were used to monitor PD and to inject current.…”