Mechanosensitive modulation of peristaltic contractions in the mouse renal pelvis

Yoshikawa, Mikako; Mitsui, Retsu; Takano, Haruo; Hashitani, Hikaru

doi:10.1016/j.ejphar.2022.174834

Cited by 5 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 5-HT-induced phasic contractions may be different from the SPCs driven by pacemaker cells in the renal pelvis that underlie pyeloureteric peristalsis. 37 Third, investigations into different PDE-4 isoenzymes will also be beneficial to identify more specific targets. Considering piclamilast was not as effective as rolipram and roflumilast in attenuating ureteral contraction, and it is likely that specific PDE-4 isoenzymes are functional in the ureter.…”

Section: Discussionmentioning

confidence: 99%

“…Second, the in vitro experimental setup may not fully recapitulate the complex in vivo physiological environment, and additional studies using in vivo models are warranted to better understand the therapeutic potential of these PDE inhibitors. The 5‐HT‐induced phasic contractions may be different from the SPCs driven by pacemaker cells in the renal pelvis that underlie pyeloureteric peristalsis 37 . Third, investigations into different PDE‐4 isoenzymes will also be beneficial to identify more specific targets.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions

Lim,

Masutani,

Hashitani

et al. 2024

Pharmacology Res & Perspec

Self Cite

View full text Add to dashboard Cite

The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre‐contracted with 5‐HT (100 μM). Upon generation of stable phasic contractions, PDE‐4 and PDE‐5 inhibitors were added cumulatively to separate tissues. PDE‐4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, while a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressant effect. The attenuation effect by rolipram was abolished by SQ22536 (100 μM). PDE‐5 inhibitors, such as sildenafil and tadalafil, were not nearly as effective and were only able to suppress the 5‐HT‐induced contractions at higher concentrations of 1 μM. Rolipram significantly enhanced the depressant effect of forskolin, while sodium nitroprusside‐induced attenuation of contractile responses remained unchanged in the presence of tadalafil. In summary, our study demonstrates that PDE‐4 inhibitors are effective in attenuating 5‐HT‐induced contractility in porcine distal ureteral tissues, while PDE‐5 inhibitors are less effective. These findings suggest that PDE‐4 inhibitors, such as rolipram, may hold promise as potential therapeutic agents for the treatment of ureteral disorders attributable to increased intra‐ureteral pressure.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions

Lim,

Masutani,

Hashitani

et al. 2024

Pharmacology Res & Perspec

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our preparations maintain coupling between the proximal and distal RP, a feature typically missing in muscle strip studies. However, whilst other studies have carried out experiments with the RP intact 26 , 27 , 31 , 66 , our SMC-GCaMP3 assay provides greater spatial and temporal resolution to track propagating Ca 2+ waves associated with contraction from the proximal RP through to the ureter. Our experiments have revealed novel and variable effects of L-type Ca 2+ channel antagonists, nicardipine and isradipine, that seem likely due to different contributions of voltage-gated Ca 2+ channels and effects of isradipine on T-type Ca 2+ channels.…”

Section: Discussionmentioning

confidence: 99%

Propagation of Pacemaker Activity and Peristaltic Contractions in the Mouse Renal Pelvis Rely on Ca2+-activated Cl− Channels and T-Type Ca2+ Channels

et al. 2022

View full text Add to dashboard Cite

The process of urine removal from the kidney occurs via the renal pelvis. The renal pelvis demarcates the beginning of the upper urinary tract and is endowed with smooth muscle cells. Along the renal pelvis, organized contraction of smooth muscle cells generates the force required to move urine boluses towards the ureters and bladder. This process is mediated by specialized pacemaker cells that are highly expressed in the proximal renal pelvis that generate spontaneous rhythmic electrical activity to drive smooth muscle depolarization. The mechanisms by which peristaltic contractions propagate from the proximal to distal renal pelvis are not fully understood. In this study, we utilized a transgenic mouse that expresses the genetically encoded Ca2+ indicator, GCaMP3, under a myosin heavy chain promotor to visualize spreading peristaltic contractions in high spatial detail. Using this approach, we discovered variable effects of L-type Ca2+ channel antagonists on contraction parameters. Inhibition of T-Type Ca2+ channels reduced the frequency and propagation distance of contractions. Similarly, antagonizing Ca2+-activated Cl− channels or altering the transmembrane Cl− gradient decreased contractile frequency and significantly inhibited peristaltic propagation. These data suggest that voltage gated Ca2+ channels are important determinants of contraction initiation and maintain the fidelity of peristalsis as the spreading contraction moves further towards the ureter. Recruitment of Ca2+-activated Cl− channels, likely Anoctamin-1, and T-Type Ca2+ channels are required for efficiently conducting the depolarizing current throughout the length of the renal pelvis. These mechanisms are necessary for the efficient removal of urine from the kidney.

show abstract

“…Notoriously, podocyte injury or TRPV1-V4 derangement leads to different glomerular diseases with consequent massive proteinuria [20]; hence, therapeutic modulation of these receptors by capsaicin could theoretically represent a potential therapeutic target for this kind of renal disease. Likewise, the TRP melastatin channels (TRPM2) are present in the cytoplasm and intracellular organelles of renal tubular cells, and their inhibition may improve the outcome of experimentally induced renal ischemia [21]. Capsaicin was also proved to modulate the integrity of tight junctions of Canine Kidney-C7 epithelial cells [22], enhancing their permeability to poorly adsorbable molecules.…”

Section: Functional and Structural Effects Of Capsaicin On The Kidneymentioning

confidence: 99%

“…Such an effect would rely upon a decrease in the perfusion pressure, driven by an enhanced vaso-relaxation mediated by the calcitonin gene-related peptide (CGRP) and the substance P, two largely acknowledged powerful vasodilators [24]. The key role of CGRP was also confirmed by another experimental model [21]. A wire myograph was employed to measure isometric tension changes in the renal tubules of mice while mechanic stimuli were applied to the pelvicalyceal junction.…”

Section: Functional and Structural Effects Of Capsaicin On The Kidneymentioning

confidence: 99%

Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and Disease

Musolino,

D’Agostino,

Zicarelli

et al. 2024

IJMS

View full text Add to dashboard Cite

Capsaicin, the organic compound which attributes the spicy flavor and taste of red peppers and chili peppers, has been extensively studied for centuries as a potential natural remedy for the treatment of several illnesses. Indeed, this compound exerts well-known systemic pleiotropic effects and may thus bring important benefits against various pathological conditions like neuropathic pain, rhinitis, itching, or chronic inflammation. Yet, little is known about the possible biological activity of capsaicin at the kidney level, as this aspect has only been addressed by sparse experimental investigations. In this paper, we aimed to review the available evidence focusing specifically on the effects of capsaicin on renal physiology, as well as its potential benefits for the treatment of various kidney disorders. Capsaicin may indeed modulate various aspects of renal function and renal nervous activity. On the other hand, the observed experimental benefits in preventing acute kidney injury, slowing down the progression of diabetic and chronic kidney disease, ameliorating hypertension, and even delaying renal cancer growth may set the stage for future human trials of capsaicin administration as an adjuvant or preventive therapy for different, difficult-to-treat renal diseases.

show abstract

Mechanosensitive modulation of peristaltic contractions in the mouse renal pelvis

Cited by 5 publications

References 19 publications

Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions

Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions

Propagation of Pacemaker Activity and Peristaltic Contractions in the Mouse Renal Pelvis Rely on Ca2+-activated Cl− Channels and T-Type Ca2+ Channels

Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and Disease

Contact Info

Product

Resources

About