Mediators of the secretory response to kinins

Abstract

1 The output of immunoreactive (i) 6 keto prostaglandin Fl, (i6ketoPGF1,). iPGE2 and ithromboxane B2 (iTXB2) from isolated colonic epithelium of the rat into the apical and basolateral bathing solution has been measured. In some instances tissues were also voltage clamped at 0 mV to measure short circuit current (SCC). 2 Kallidin (lysylbradykinin) stimulated the output of all three eicosanoids, specifically from the basolateral face of the tissue. The output was similar whether or not the tissues were short circuited. 3 Both the SCC response and eicosanoid output were dependent upon the concentration of kallidin, but not in a strictly proportional manner, there being relatively more eicosanoid output at submaximal kinin concentrations. 4 Indomethacin, 5 JiM, abolished the eicosanoid output, in response to kinin, while some part of the SCC response remained. 5 Calcium removal from the basolateral bathing fluid severely attenuated the SCC response, reduced the output of i6ketoPGFp, to half, but left the output of iPGE2 unchanged. In the presence or absence of calcium it is probable that sufficient PGE material is released to cause part of the SCC changes seen with kinin. 6 Kinin and PGE1 increased the cyclic AMP content of intact epithelia, provided a phosphodiesterase inhibitor was added at the same time.7 It is proposed that kinin causes an increase in calcium influx at the basolateral pole of the tissue. This calcium is necessary for the production of some eicosanoids and the subsequent generation of cyclic AMP, which then increases apical chloride permeability. In addition, calcium may facilitate entry of chloride through the basolateral face of the cells by activating a cotransport mechanism.

Electrogenic anion secretion in cultured rat epididymal epithelium.

“…In rat colon, kinin responses have been shown to be partially dependent upon eicosanoid formation (Cuthbert, Halushka, Margolius & Spayne, 1984b;Cuthbert, Halushka, Kessel, Margolius & Wise, 1984a) whereas in the epididymis the response to kinin on the basolateral side is completely abolished by piroxicam and indomethacin. Chronic treatment with PGE2 caused reduced fertility in male rats (Hib, Ponzio & Vilar, 1979) and the suggested mechanism was reduced sperm transit time caused by increased epididymal motility; thus the time available for sperm maturation was reduced.…”

Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon

“…Previously, PGE 2 release elicited by AITC (10 Ϫ4 M) has been reported in rat urinary bladder (3). In addition, other inflammatory mediator kinins are known to induce Cl Ϫ secretion through PGE 2 release in the colon (6, 36) independent of extracellular Ca 2ϩ (13). In the present study, we demonstrated that AITC-evoked anion secretion was independent of neural activity or extracellular Ca 2ϩ ( Table 3), suggesting that AITC-evoked anion secretion is mediated by PG release through a Ca 2ϩ -independent process.…”

Antagonism of kinin effects on epithelia by Hoe 140: apparently competitive and non‐competitive interactions

“…Inhibition of eicosanoid synthesis does not affect the calcium signal but severely attenuates the SCC response. Prostaglandins activate epithelial adenylate cyclase (Cuthbert et al, 1984) which in turn causes apical chloride channels to open (Henderson et al, 1992). Furthermore in Colony 29 epithelial cells, calcium release from intracellular stores provokes a further calcium influx from outside the cell .…”