Platelet-activating factor (PAF) strongly enhances contractile mechanical activities in guinea pig and mouse urinary bladder

Mizuki Kaneko,Yoshio Tanaka,Keisuke Obara,Ge Liu,Kento Yoshioka

doi:10.1038/s41598-022-06535-7

Mizuki Kaneko, Yoshio Tanaka + Show 3 more

Open Access

https://doi.org/10.1038/s41598-022-06535-7

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Journal: Scientific Reports	Publication Date: Feb 17, 2022
Citations: 6	License type: open-access

Affiliation: Toho University

Abstract

In this study, we investigated the effects of platelet-activating factor (PAF) on the basal tone and spontaneous contractile activities of guinea pig (GP) and mouse urinary bladder (UB) smooth muscle (UBSM) tissues to determine whether PAF could induce UBSM tissue contraction. In addition, we examined the mRNA expression of the PAF receptor, PAF-synthesizing enzyme (lysophosphatidylcholine acyltransferase, LPCAT), and PAF-degrading enzyme (PAF acetylhydrolase, PAF-AH) in GP and mouse UB tissues using RT-qPCR. PAF (10−9–10−6 M) strongly enhanced the basal tone and spontaneous contractile activities (amplitude and frequency) of GP and mouse UBSM tissues in a concentration-dependent manner. The enhancing effects of PAF (10−6 M) on both GP and mouse UBSM contractile activities were strongly suppressed by pretreatment with apafant (a PAF receptor antagonist, GP: 10−5 M; mouse: 3 × 10−5 M). The PAF receptor (Ptafr), LPCAT (Lpcat1, Lpcat2), and PAF-AH (Pafah1b3, Pafah2) mRNAs were detected in GP and mouse UB tissues. These findings reveal that PAF strongly enhances the contractile mechanical activities of UBSM tissues through its receptor and suggest that the PAF-synthesizing and -degrading system exists in UBSM tissues. PAF may serve as both an endogenous UBSM constrictor and an endogenous mediator leading to detrusor overactivity.

Highlights

Platelet-activating factor (PAF) is a powerful mediator of inflammation and allergies
We examined mRNA expression of the platelet-activating factor (PAF) receptor, PAF-synthesizing enzyme [lysophosphatidylcholine acyltransferase (LPCAT)], and PAF-degrading enzyme [PAF acetylhydrolase (PAF-AH)] in guinea pig (GP) and mouse urinary bladder (UB) tissues to further understand whether PAF acts as an endogenous regulator of UBSM mechanical activities
We found that PAF ( 10−9–10−6 M) strongly enhanced the basal tone and spontaneous contractile activities of GP and mouse UBSM tissues in a concentration-dependent manner

Summary

Introduction

Platelet-activating factor (PAF) is a powerful mediator of inflammation and allergies. The accumulation of PAF caused by smoking was reported in urinary bladder (UB) microvascular endothelial cells and urothelial cells, which suggests that PAF plays an important role in the development of chronic inflammatory UB diseases, such as interstitial cystitis and UB pain syndrome[21,22]. The accumulation of PAF was significantly higher in isolated urothelial tissues from bladder cancer patients than in normal human urothelial tissues, and PAF expression was markedly increased in high-grade tumors compared with low-grade tumors[23]. These findings suggest that increased PAF production in urothelial cells is associated with lower urinary tract diseases. We examined mRNA expression of the PAF receptor, PAF-synthesizing enzyme [lysophosphatidylcholine acyltransferase (LPCAT)], and PAF-degrading enzyme [PAF acetylhydrolase (PAF-AH)] in GP and mouse UB tissues to further understand whether PAF acts as an endogenous regulator of UBSM mechanical activities

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