The authors declare that they have no competing interests.
JAH - conception and design, analysis and interpretation of the data, drafting of the manuscript. APM - general supervision, critical revision for intellectual content. All authors have made a significant contribution to the paper, and have read and approved the final draft.
Protein kinase C (PKC) is expressed in many tissues and organs including the urinary bladder, however, its role in bladder physiology and pathophysiology is still evolving. The aim of this review was to evaluate available evidence on the involvement of PKC in regulation of detrusor contractility, muscle tone of the bladder wall, spontaneous contractile activity and bladder function under physiological and pathophysiological conditions.
This is a non-systematic review of the published literature which summarizes the available animal and human data on the role of PKC signaling in the urinary bladder under different physiological and pathophysiological conditions. A wide PubMed search was performed including the combination of the following keywords: “urinary bladder”, “PKC”, “detrusor contractility”, “bladder smooth muscle”, “detrusor relaxation”, “peak force”, “detrusor underactivity”, “partial bladder outlet obstruction”, “voltage-gated channels”, “bladder nerves”, “PKC inhibitors”, “PKC activators”. Retrieved articles were individually screened for the relevance to the topic of this review with 91 citations being selected and included in the data analysis.
Urinary bladder function includes the ability to store urine at low intravesical pressure followed by a subsequent release of bladder contents due to a rapid phasic contraction that is maintained long enough to ensure complete emptying. This review summarizes the current concepts regarding the potential contribution of PKC to contractility, physiological voiding, and related signaling mechanisms involved in the control of both the storage and emptying phases of the micturition cycle, and in dysfunctional voiding. Previous studies linked PKC activation exclusively with an increase in generation of the peak force of smooth muscle contraction, and maximum force generation in the lower urinary tract. More recent data suggests that PKC presents a broader range of effects on urinary bladder function including regulation of storage, emptying, excitability of the detrusor, and bladder innervation.
In this review, we evaluated the mechanisms of peripheral and local regulation of PKC signaling in the urinary bladder, and their impact on different phases of the micturition cycle under physiological and pathophysiological conditions.
Levin RM, Ruggieri MR, Velagapudi S, Gordon D, Altman B, Wein AJ. Relevance of spontaneous activity to urinary bladder function: an in vitro and in vivo study. J Urol. 1986;136(2):517–21. PubMed
Wein AJ. Physiology of micturition. Clin Geriatr Med. 1986;2(4):689–99. PubMed
Dessy C, Kim I, Sougnez CL, Laporte R, Morgan KG. A role for MAP kinase in differentiated smooth muscle contraction evoked by alpha-adrenoceptor stimulation. Am J Physiol. 1998;275(4 Pt 1):C1081–1086. PubMed
Caulfield MP, Birdsall NJ. International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev. 1998;50(2):279–90. PubMed
Petkov GV. Role of potassium ion channels in detrusor smooth muscle function and dysfunction. Nat Rev Urol. 2012;9(1):30–40. CrossRef
Zderic SA, Sillen U, Liu GH, Snyder 3rd MC, Duckett JW, Gong C, et al. Developmental aspects of excitation contraction coupling of rabbit bladder smooth muscle. J Urol. 1994;152(2 Pt 2):679–81. PubMed
Herrera GM, Heppner TJ, Nelson MT. Regulation of urinary bladder smooth muscle contractions by ryanodine receptors and BK and SK channels. Am J Physiol Regul Integr Comp Physiol. 2000;279(1):R60–68. PubMed
Bonev AD, Nelson MT. ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. Am J Physiol. 1993;264(5 Pt 1):C1190–1200. PubMed
Gopalakrishnan M, Whiteaker KL, Molinari EJ, Davis-Taber R, Scott VE, Shieh CC, et al. Characterization of the ATP-sensitive potassium channels (KATP) expressed in guinea pig bladder smooth muscle cells. J Pharmacol Exp Ther. 1999;289(1):551–8. PubMed
Malmgren A, Andersson KE, Sjogren C, Andersson PO. Effects of pinacidil and cromakalim (BRL 34915) on bladder function in rats with detrusor instability. J Urol. 1989;142(4):1134–8. PubMed
Bonev AD, Nelson MT. Muscarinic inhibition of ATP-sensitive K+ channels by protein kinase C in urinary bladder smooth muscle. Am J Physiol. 1993;265(6 Pt 1):C1723–1728. PubMed
Eto M, Ohmori T, Suzuki M, Furuya K, Morita F. A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J Biochem. 1995;118(6):1104–7. PubMed
Hristov KL, Parajuli SP, Soder RP, Cheng Q, Rovner ES, Petkov GV. Suppression of human detrusor smooth muscle excitability and contractility via pharmacological activation of large conductance Ca2 + −activated K+ channels. Am J Physiol Cell Physiol. 2012;302(11):C1632–1641. PubMedCentralCrossRefPubMed
Brading AF. Ion channels and control of contractile activity in urinary bladder smooth muscle. Jpn J Pharmacol. 1992;58 Suppl 2:120P–7P. PubMed
Parajuli SP, Hristov KL, Cheng Q, Malysz J, Rovner ES, Petkov GV. Functional link between muscarinic receptors and large-conductance Ca-activated K channels in freshly isolated human detrusor smooth muscle cells. Pflugers Archiv. 2015;467(4):665-75. doi: 10.1007/s00424-014-1537-8. Epub 2014 May 28.
Levin RM, Monson FC, Haugaard N, Buttyan R, Hudson A, Roelofs M, et al. Genetic and cellular characteristics of bladder outlet obstruction. Urol Clin North Am. 1995;22(2):263–83. PubMed
Shahab N, Kajioka S, Takahashi-Yanaga F, Onimaru M, Matsuda M, Seki N, et al. Obstruction enhances rho-kinase pathway and diminishes protein kinase C pathway in carbachol-induced calcium sensitization in contraction of alpha-toxin permeabilized guinea pig detrusor smooth muscle. Neurourol Urodyn. 2012;31(4):593–9. CrossRefPubMed
Choi BH, Jin LH, Kim KH, Kang SA, Kang JH, Yoon SM, et al. Cystometric parameters and the activity of signaling proteins in association with the compensation or decompensation of bladder function in an animal experimental model of partial bladder outlet obstruction. Int J Mol Med. 2013;32(6):1435–41. PubMed
Sadler KE, Stratton JM, Kolber BJ. Urinary bladder distention evoked visceromotor responses as a model for bladder pain in mice. J Vis Exp. 2014:(86).
- Regulation of urinary bladder function by protein kinase C in physiology and pathophysiology
Joseph A. Hypolite
Anna P. Malykhina
- BioMed Central
Neu im Fachgebiet Urologie
Meistgelesene Bücher in der Urologie
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