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

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.

Upregulation of Platelet-Activating Factor Receptor Expression and Lyso-Platelet-Activating Factor Isoforms in Human Nasal Polyp Tissues

“…PAF is synthesized by multiple cells of the immune system, especially eosinophils, neutrophils, and mast cells. However, PAF is not only produced in inflammatory cells but also by structural cells, such as cardiomyocytes, vascular endothelial cells, urothelial cells, and airway epithelial cells [1,3,4]. In fact, upon the PAF being generated, it can act upon the cell itself or to neighboring cells in a juxtracrine fashion [3].…”

OMICS Analyses Unraveling Related Gene and Protein-Driven Molecular Mechanisms Underlying PACAP 38-Induced Neurite Outgrowth in PC12 Cells

“…Similarly, AGTR1A down-regulated at 5 min and AGTR1B down-regulated at 30 min are also activated by the vasoconstrictor peptide angiotensin II. PTAFR, down-regulated at 15 min, is a platelet-activating factor (PAF) receptor, and PAF not only aggregates and activates platelets and white blood cells, but also decreases blood pressure and induces biological activities, such as tracheal contraction [ 55 ].…”

Pharmacological Studies on the Ca²⁺ Influx Pathways in Platelet-Activating Factor (PAF)-Induced Mouse Urinary Bladder Smooth Muscle Contraction

“…Measurement of PAF-Induced BTI and OC in Mouse UBSM PAF-induced BTI/OC were isometrically measured according to a previous report. 12) Briefly, UBSM strips were suspended under resting tension (0.5 g) in a 20 mL organ bath filled with Locke-Ringer solution containing (mM) NaCl, 154; KCl, 5.63; CaCl 2 , 2.16; MgCl 2 , 2.1; NaHCO 3 , 5.95; and glucose, 2.78. The solution was stored at 32 ± 1.0 °C and bubbled with a mixture of 95% O 2 /5% CO 2 .…”

“…Data Analysis PAF-induced BTI and the amplitude/ frequency of PAF-induced OC were analyzed as previously reported. 12,16) Briefly, BTI/OC were calculated over 3 min using the LabChart™ (Version 7) software (ADInstruments Pty. Ltd., Bella Vista, NSW, Australia): immediately before…”

“…10,11) In addition to these SMs, PAF was previously found to induce basal tension increase (BTI) and oscillatory contraction (OC) in mouse urinary bladder (UB) SM (UBSM). 12) Although PAF-induced contractile responses in gastrointestinal and pregnant uterine SMs were demonstrated to depend on Ca 2+ influx via voltage-dependent Ca 2+ channel (VDCC), [3][4][5]10) the dependence of Ca 2+ influx on PAF-induced BTI/OC in mouse UBSM and these Ca 2+ influx pathways remain unclear. We examined the Ca 2+ influx pathway involved in PAF-induced BTI/OC in mouse UBSM.…”