Biphasic short-circuit current response to noradrenaline mediated by Ca2+ and cAMP in cultured rat epididymal epithelium

Leung, Ares; Wong, Patrick

doi:10.1007/bf00388302

Cited by 11 publications

(16 citation statements)

References 23 publications

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“…In the present study, we also found that ATP significantly increased cellular cAMP and that this increase could be prevented by chelating intracellular Ca2+ with BAPTA-AM (100 pM). At this concentration BAPTA has been reported to suppress various Ca2+-dependent Is, responses (Leung and Wong, 1994;Lai et al, 1994). It should be noted that in the present study BAPTA at the same concentration did not affect forskolin-induced cAMP production.…”

Section: Discussionmentioning

confidence: 58%

Different regulatory pathways involved in ATP‐stimulated chloride secretion in rat epididymal epithelium

Chan

Zhou

et al. 1995

Journal Cellular Physiology

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The regulatory pathways involved in the ATP-stimulated Cl- secretion across rat epididymal epithelium were investigated by the short-circuit current (ISC) technique. Biphasic characteristic was observed in the ISC responded to ATP (0.01-10 microM). Inhibitor of P1 receptor, 8-phenyltheophylline (up to 100 microM), did not have any effect on both phases of the ATP-stimulated ISC. The order of potency for stimulation of the two phases in ISC was ATP > ADP >> AMP, adenosine, consistent with the presence of P2-purinoceptors. Cl- channel blocker, disulfonic acid stilbene (DIDS, 300 microM), only inhibited the first peak of the ATP-stimulated ISC while diphenylamine-dicarboxylic acid (DPC, 1 mM) reduced both, indicating the involvement of different conductance pathways. DIDS was found to have an inhibitory effect on Ca(2+)-activated ISC (induced by ionomycin, 10 microM) but not cAMP-activated ISC (induced by forskolin, 1 microM) which could only be blocked by DPC. Both peaks of the ATP-activated ISC could be significantly inhibited by pretreatment with a Ca(2+)-chelating agent, BAPTA-AM (50 microM). An increase in cellular cAMP content upon stimulation of ATP was measured by radioimmunoassay. No significant increase in cAMP production was observed in cells stimulated with adenosine. The ATP-induced cAMP increase was prevented by pretreatment with BAPTA-AM (100 microM) indicating that cAMP production upon ATP stimulation was secondary to an increase in intracellular Ca2+ concentration. These results indicate that the ATP-stimulated Cl- secretion could be mediated by Ca2+ and cAMP-dependent regulatory pathways giving rise to the biphasic nature of the ATP-induced ISC.

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Section: Discussionmentioning

confidence: 58%

Different regulatory pathways involved in ATP‐stimulated chloride secretion in rat epididymal epithelium

Chan

Zhou

et al. 1995

Journal Cellular Physiology

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“…The former has been shown to transduce the signals from purinoceptors (Wong, 1988b) and the latter from b-adrenoceptors (Chan et al, 1994;Leung and Wong, 1994) and PGE 2 receptors . Pharmacological agents have been used to perturb these pathways with an aim to delineate the second messenger pathways involved in neurohumoral stimulation of secretion Leung and Wong, 2000).…”

Section: Discussionmentioning

confidence: 99%

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

Cheuk

Wong

2002

Journal Cellular Physiology

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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.

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“…An increase in intracellular Ca 2þ was observed after addition of 100 lM DA. This increase in intracellular Ca 2þ was rapid and appeared to be an extracellular Ca 2þ -dependent response [5,27]. When cells were bathed in a Ca 2þ -free saline solution, DA did not induce any change in intracellular Ca 2þ .…”

Section: Discussionmentioning

confidence: 97%

“…Dopamine-induced Isc initial response is mediated by areceptor stimulation, and the secondary sustained response is mediated by beta-receptor activation. The Cl À secretion mediated by adrenoreceptor activation in cultured rat epididymal epithelial cells has already been studied in response to other neurotransmitters [5,18,19]. Phentolamine inhibited the a 1 -adrenoreceptor-mediated Cl À secretion (initial spike), whereas propranolol inhibited the b 1 , b 2 -mediated Cl À secretions (second phase) in a dose-dependent fashion [19].…”

Section: Discussionmentioning

confidence: 98%

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Stimulating Effects of Dopamine on Chloride Transport Across the Rat Caudal Epididymal Epithelium in Culture1

Zuo

Ruan

et al. 2009

Biology of Reproduction

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The present study investigated the effects of dopamine on chloride transport across cultured rat caudal epididymal epithelium. The results showed that dopamine induced a biphasic short-circuit current (Isc) in a concentration-dependent manner. The dopamine-induced response consisted of an initial rapid spike followed by a sustained phase. The alpha and beta adrenoreceptor inhibitors, phentolamine and propranolol, inhibited the initial spike and the sustained phase, respectively, suggesting a contribution of adrenergic receptors. The response was almost abolished by removing the extracellular Cl-, suggesting that the dopamine-induced short-circuit current is primarily a Cl- current. The response was inhibited by the apical Cl- channel blocker, diphenylamine-dicarboxylic acid, and the Ca2+-activated Cl- channel blocker, disulfonic acid stilbene, indicating that Cl- may pass through two types of Cl- channels on the apical side. Preloading monolayers with the intracellular Ca2+ chelator BAPTA/AM abolished the initial spike and greatly reduced the second phase in the Isc response to dopamine. Pretreating the monolayers with an adenylate cyclase inhibitor, MDL12330A, inhibited all of the second Isc response and part of the initial spike. Also, characteristics of the Cl- currents induced by dopamine were observed in whole-cell patch-clamp recording. The increases of intracellular cAMP and Ca2+ induced by dopamine were also measured. The results suggest that extracellular dopamine activates Ca2+-dependent and cAMP-dependent regulatory pathways, leading to activation of both Ca2+-dependent and cAMP-dependent Cl- conductances in epididymal epithelial cells.

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Biphasic short-circuit current response to noradrenaline mediated by Ca2+ and cAMP in cultured rat epididymal epithelium

Cited by 11 publications

References 23 publications

Different regulatory pathways involved in ATP‐stimulated chloride secretion in rat epididymal epithelium

Different regulatory pathways involved in ATP‐stimulated chloride secretion in rat epididymal epithelium

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

Stimulating Effects of Dopamine on Chloride Transport Across the Rat Caudal Epididymal Epithelium in Culture1

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