Transcriptome Characterization of Estrogen-Treated Human Myocardium Identifies MYLIP as a Sex- Specific Element Influencing Contractile Function.

status: publishe

Calcium-induced calcium release participates in cell volume regulation of rabbit TALH cells

Changes of cell volume and intracellular calcium concentration ([Ca2+](i)) in immortalized thick ascending limb of Henle's loop (TALH) cells were monitored using confocal laser scanning microscopy and fura-2 fluorescence, respectively, Reduction of the extracellular osmolarity from 600 to 300 mosmol/l induced cell swelling followed by regulatory volume decrease (RVD). Simultaneously, the [Ca2+](i) increased transiently. The calcium rise was not observed in calcium-free solution or in the presence of nifedipine, indicating that the change was, in the first place, due to the activation of a calcium influx. Application of ATP or caffeine in isotonic solutions increased transiently the [Ca2+](i), which revealed the existence of stores in TALH cells sensitive to inositol-1,4,5 trisphosphate (IP3) and ryanodine. To examine the possibility that the calcium influx might induce calcium release, manganese quenching experiments were performed. In hypotonic calcium-free solutions, the decay of the calcium-insensitive and calcium- sensitive fluorescence occurred simultaneously. In the presence of extracellular calcium however, the calcium-sensitive wavelength revealed initial calcium influx followed by a calcium release from intracellular stores. Thus, the calcium influx was a prerequisite for the calcium release. We conclude that calcium-induced calcium release participates in global calcium signalling during RVD of TALH cells

Effects of PDE5 Inhibitors and sGC Stimulators in a Rat Model of Artificial Ureteral Calculosis

<div><p>Urinary colics from calculosis are frequent and intense forms of pain whose current pharmacological treatment remains unsatisfactory. New and more effective drugs are needed to control symptoms and improve stone expulsion. Recent evidence suggested that the Nitric Oxide (NO) / cyclic guanosine monophosphate (cGMP) / phosphodiesterase type 5 (PDE5) system may contribute to ureteral motility influencing stone expulsion. We investigated if PDE5 inhibitors and sGC stimulators influence ureteral contractility, pain behaviour and stone expulsion in a rat model of ureteral calculosis. We investigated: a)the sex-specific PDE5 distribution in the rat ureter; b)the functional <i>in vitro</i> effects of vardenafil and sildenafil (PDE5 inhibitors) and BAY41-2272 (sGC stimulator) on induced ureteral contractility in rats and c)the <i>in vivo</i> effectiveness of vardenafil and BAY41-2272, alone and combined with ketoprofen, vs hyoscine-N-butylbromide alone or combined with ketoprofen, on behavioural pain indicators and stone expulsion in rats with artificial calculosis in one ureter. PDE5 was abundantly expressed in male and female rats’ ureter. <i>In vitro</i>, both vardenafil and BAY41-2272 significantly relaxed pre-contracted ureteral strips. <i>In vivo</i>, all compounds significantly reduced number and global duration of “ureteral crises” and post-stone lumbar muscle hyperalgesia in calculosis rats. The highest level of reduction of the pain behaviour was observed with BAY41-2272 among all spasmolytics administered alone, and with the combination of ketoprofen with BAY41-2272. The percentage of stone expulsion was maximal in the ketoprofen+BAY41-2272 group. The NO/cGMP/PDE5 pathway is involved in the regulation of ureteral contractility and pain behaviour in urinary calculosis. PDE5 inhibitors and sGC stimulators could become a potent new option for treatment of urinary colic pain.</p></div

Ureteral pain behaviour.

<p>Global duration of crises. Legend as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141477#pone.0141477.g004" target="_blank">Fig 4</a> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141477#pone.0141477.s002" target="_blank">S2 File</a>).</p