Rapid responses to aldosterone in human distal colon

Maguire, Donal; MacNamara, Brian; Cuffe, John E.; Winter, Desmond C.; Doolan, Christina M.; Urbach, V.; O’Sullivan, Gerald C.; Harvey, Bill

doi:10.1016/s0039-128x(98)00096-8

Cited by 63 publications

(77 citation statements)

References 22 publications

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“…Although the significance of this increase in diastolic calcium is not yet known, this finding is similar to the 80 nmol/L increase in intracellular calcium reported in human bronchial epithelial cells elicited by spironolactone. 21 Unlike aldosterone, spironolactone also did not alter the pCa 50 . However, in contrast, spironolactone produced a maximal ATPase response, which was 2.4-fold higher than that seen with aldosterone.…”

Section: Discussionmentioning

confidence: 92%

“…However, compared with control, aldosterone was without effect on the Hill coefficient (2.2Ϯ0.2 versus 2.1Ϯ0.4). Conversely, myofibrils obtained from spironolactoneperfused hearts produced similar pCa 50 relative to vehicle controls (pCa 50 ϭ5.8Ϯ0.3 versus 5.8Ϯ0.1; Figure 6a). However, spironolactone significantly increased the Hill coefficient (Hill coefficientϭ2.2Ϯ0.2 versus 3.1Ϯ0.3, PϽ0.01).…”

Section: Myofibrillar Atpasementioning

confidence: 88%

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Mechanisms for Aldosterone and Spironolactone-Induced Positive Inotropic Actions in the Rat Heart

et al. 2004

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Abstract-Previously, we reported that aldosterone and spironolactone have inotropic effects in the isolated perfused heart.To address the mechanisms underlying these inotropic effects, we examined the effects of aldosterone and spironolactone on isolated cardiac myocyte shortening, intracellular calcium ( ). Collectively, these data strongly suggest that the inotropic actions of aldosterone and spironolactone are caused by different mechanisms of action. Aldosterone appeared to increase inotropy primarily through increased cytosolic pH, whereas spironolactone increased myosin ATPase calcium sensitivity and diastolic calcium concentration. Key Words: mineralocorticoid Ⅲ cardiac function Ⅲ heart failure Ⅲ calcium T he Randomized ALdactone Evaluation Study (RALES) demonstrated significant reductions in morbidity and mortality when spironolactone, the aldosterone mineralocorticoid receptor antagonist, was included in the treatment of heart failure. 1 This study, along with many translational reports, strongly developed the concept that aldosterone may play an important, deleterious effect in human congestive heart failure. [2][3][4][5] In addition, we have previously observed that aldosterone has rapid, inotropic effects in the isolated perfused rat heart; 6 however, rapid, inotropic effects were observed as early as the 1960s. 7,8 This rapid, inotropic effect of aldosterone almost certainly occurs through nongenomic mechanism(s).Nongenomic actions of aldosterone were first identified by Wehling et al in smooth muscle cells. 9 -12 These actions were classified as nongenomic because of their speed, lack of inhibition by spironolactone, and independence from new protein synthesis. Based on these characteristics, nongenomic effects of aldosterone have been reported from a number of laboratories in renal epithelial cells, 13 vascular smooth muscle cells, 14,15 skeletal muscle cells, 16 and colonic. The molecular basis of these nongenomic effects of aldosterone actions have been ascribed to changes in intracellular pH (pHi), [17][18][19] 20 -25 Although it has been observed that aldosterone does have rapid effects on protein kinase C activity in cultured cardiac cells, 26 and that aldosterone has rapid effects on cardiac sodiumhydrogen exchange, 27 the molecular mechanism of the rapid inotropic effect of aldosterone is still unclear.The spironolactone issue is less well defined and perhaps of greater interest because of the favorable results of the RALES trial. 1 We previously observed that substantial inotropy could be observed with levels of spironolactone that were comparable to those achieved with this agent in standard clinical practice. Moreover, the inotropic effect of spironolactone was found to be additive to that of aldosterone when both agents were administered together. These studies strongly suggest that although aldosterone and spironolactone are similar in structure, they have independent mechanism(s) of actions. Therefore, the objective of the present study was

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Section: Discussionmentioning

confidence: 92%

Section: Myofibrillar Atpasementioning

confidence: 88%

Mechanisms for Aldosterone and Spironolactone-Induced Positive Inotropic Actions in the Rat Heart

et al. 2004

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“…This cyclo-heximide dose has been previously shown to inhibit the genomic eect of aldosterone on potassium transport in colonic epithelium (Maguire et al, 1999). Subsequent addition of oestradiol produced an eect equivalent to that in normal controls when the current was both tolbutamide sensitive and TPeA sensitive (Table 4).…”

Section: Role Of Protein Synthesismentioning

confidence: 87%

Rapid activation of basolateral potassium transport in human colon by oestradiol

McNamara

Winter

Cuffe

et al. 2000

British J Pharmacology

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1 We investigated the eect of oestradiol on basolateral potassium channels in human colonic epithelium. 2 Ion transport was quanti®ed using short circuit current (I sc ) measurements of samples mounted in Ussing chambers. Serosal K transport was studied using nystatin permeabilization of the apical membrane. Intracellular pH changes were quanti®ed using spectro¯ouresence techniques. 3 Experiments were performed with either 10 nM or 1 mM Ca 2+ in the apical bathing solution. With 10 nM Ca 2+ in the apical bathing solution addition of oestradiol (1 nM) to the basolateral bath produced a rapid increase in current (DI K =11.2+1.2 mA.cm 72 , n=6). This response was prevented by treatment of the serosal membrane with tolbutamide (1 mM). With 1 mM Ca 2+ in the apical bathing solution addition of oestradiol produced a rapid fall in current (DI K =712.8+1.4 mA.cm 72 ), this response was prevented by treatment of the basolateral membrane with tetra-pentylammonium (TPeA). These responses were rapid and occurred independently of protein synthesis. 4 Inhibition of basolateral Na + /H + exchange with either amiloride or a low sodium bathing solution prevented this response. These responses were prevented by inhibition of protein kinase C (PKC) with bis-indolyl-maleimide. 5 Oestradiol (1 nM) produced a rapid intracellular alkanization (mean increase=0.11 pH units; n=6; P50.01). 6 These results suggest that oestradiol rapidly modulates serosal K transport in human colon. These eects depend upon intact Na + /H + exchange and protein kinase C. We propose a nonclassical, possibly membrane linked, mechanism for oestradiol action in human colonic epithelium.

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“…The physiological and clinical relevance supporting these rapid effects remains unclear, but their existence has been described in various target organs and cells, including amphibian skin and urinary bladders [258,259], vascular smooth muscle cells and endothelial cells [260], skeletal muscle cells [261], human mononuclear leukocytes [262], cardiac myocytes [263], skin fibroblasts from MR-knockout mice [256], colonic epithelial cells [264] and isolated colonic crypts [265]. Several sites in the kidney, particularly cultured kidney cells, have been shown to be sensitive to non-genomic ALDO action [266], including principal cells that were freshly isolated from rabbits [267], the human distal colon [268], in vivo renal proximal tubules (S2 segment) [228], isolated renal proximal tubules (S3 segment) [229,233], medullary thick ascending limbs [269] and renal collecting duct cells [270]. Its non-genomic actions include effects on signal transduction pathways and ion transporters, such as the epithelial Na + channel [267], the Na + /H + exchanger [228,229,271,272] and the vacuolar H + -ATPase [230,233,258,259,273].…”

Section: Non-genomic Actions Of Aldomentioning

confidence: 99%

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

Mello-Aires¹,

Dellova²,

Castelo‐Branco³

et al. 2017

Nephrol Renal Dis

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This article reviews the main body of knowledge regarding NHE1 and NHE3 exchangers and their interaction with Angiotensin II, Angiotensin-(1-7), Aldosterone and Arginine Vasopressin, particularly their renal actions. This work addresses the biphasic effects of different hormonal doses on NHE1 or NHE3 in proximal tubule in Wistar, SHR (hypertensives) and their control WKY (normotensives) rats or MDCK cells (which share similarities with the collecting duct). The hormones were applied alone, with their inhibitors or plus agents that change the [Ca 2+ ]i. The data are compatible with hormonal stimulation of these exchangers by increases of [Ca 2+ ]i in lower range, and inhibition at high [Ca 2+ ]i. In MDCK cells and Wistar rats, low doses of ANG II, ALDO or AVP stimulated the exchangers, while high doses inhibited them. ANG-(1-7), in Wistar or WKY rats has inverse, dose-dependent effects. In SHR rats, the biphasic effects of ANG-(1-7) were similar to the effects of ANG II, ALDO or AVP in Wistar rats. The interactions between these effects may represent a mechanism that regulates extracellular volume. In hypertensives animals, a high plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated hypertension. Figure 6 shows a schematic model to describe these biphasic hormonal effects.

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Rapid responses to aldosterone in human distal colon

Cited by 63 publications

References 22 publications

Mechanisms for Aldosterone and Spironolactone-Induced Positive Inotropic Actions in the Rat Heart

Mechanisms for Aldosterone and Spironolactone-Induced Positive Inotropic Actions in the Rat Heart

Rapid activation of basolateral potassium transport in human colon by oestradiol

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

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