COX‐dependent and ‐independent pathways in bradykinin‐induced anion secretion in rat epididymis

Abstract

Lysylbradykinin (LBK) added to the apical or basolateral side of cultured rat epididymal monolayers stimulated a rise in short-circuit current (Isc) due to anion secretion. The concentration-response relationships for the apical and basolateral applications have EC50 value of 0.001 microM. The responses to apical or basolateral application of LBK were blocked by WIN64338, a specific B2 receptor antagonist, but not by Des-Arg9,[Leu8]-BK, a specific B1 receptor antagonist, indicating that the LBK effects were mediated through B2 bradykinin receptors. Experiments to desensitize the B2 receptors by repeated stimulation have demonstrated that the responses to apical or basolateral LBK were due to discrete receptors on the apical or basolateral surface. In epithelia clamped in the Ussing chambers, addition of LBK to the apical or basolateral surface evoked release of PGE2 into the apical and basolateral bathing solutions over the first 10 min following hormone addition. LBK added to the basolateral side elicited a greater release than it was added to the apical side. Pretreatment of the epithelia with piroxicam (5 microM) abolished PGE2 release elicited by apical or basolateral LBK and abrogated the Isc induced by basolateral LBK. However, the rise in Isc induced by apical LBK was reduced by 31.3% only. The anion secretion response to apical LBK was not affected by MDL-12330A, an adenylate cyclase inhibitor, but greatly attenuated by thapsigargin, an inhibitor of intracellular Ca2+ release. However, the reverse effects were seen for basolateral LBK. It is concluded that distinct pathways are involved in the stimulation of anion secretion by apical or basolateral LBK. The response to basolateral LBK was COX-dependent, mediated by PGE2 and involves cAMP as second messenger. In contrast, the response to apical LBK is largely COX-independent, not mediated by PCE2 and involves Ca2+ as intracellular messenger.

P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport

“…Thus, a large part of the UDP-mediated stimulation of Cl -secretion apparently occurs through the generation of prostaglandins and a subsequent stimulation of an epithelial cAMP increase. In analogy to other epithelial organs where prostaglandin release was shown to originate form epithelial cells, we suggest that a similar phenomenon is true in colonic mucosa (26,30). Our results, however, do not rule out whether, in addition to a "direct" epithelial effects, other subepithelial cells (e.g., immunocytes) contribute in an "indirect" way to the observed UDP-stimulated secretion.…”

Modulation of tyramine signaling by osmolality in an insect secretory epithelium

“…Such effects result in rapid modulation of epithelial function by osmolality, just as in the MTs, but the MTs respond to changes in osmolality in a fundamentally different way then has been reported for other epithelia. It is intriguing to note the numerous examples of secretory epithelia that are under the control of biogenic amines and other hormones (2,10,11,20,30,47,52). The current data raise the possibility that some of these signaling pathways might also be modulated by osmolality just as is tyramine signaling in the MTs.…”

Cellular Mechanisms of Carbachol-Stimulated Cl− Secretion in Rat Epididymal Epithelium1

“…As with other ion channels on the membrane, CFTR was controllable by pharmacological agents, such as noradrenalin [1], lysylbradykinin (LBK) [9], and PACAP [2]. However, the physiological functions of CFTR and CLCAs that are regulated by CCH have not been shown.…”

“…Previous studies reported that various neurohormonal agents, including adrenaline, bradykinin, gastrin-releasing peptide, and prostaglandin E 2 and F 2a , are effective stimulants of electrogenic transport across epididymal epithelia of a number of species [9,10]. The cellular mechanisms, e.g., transporters and ion channels, underlying these responses have been elucidated, but the mechanisms of CCH-induced Cl À secretion by epididymis has not been shown.…”