Platelet-activating factor (PAF) enhances guinea pig detrusor smooth muscle contractile activities by stimulating voltage-dependent Ca2+ channels and store-operated Ca2+ channels

Keisuke Obara; Mizuki Kaneko; Mio Yamashita; Ge Liu; Kento Yoshioka; Yoshio Tanaka

doi:10.1016/j.jphs.2023.04.004

Platelet-activating factor (PAF) enhances guinea pig detrusor smooth muscle contractile activities by stimulating voltage-dependent Ca²⁺ channels and store-operated Ca²⁺ channels

J Pharmacol Sci. 2023 Jun;152(2):123-127. doi: 10.1016/j.jphs.2023.04.004. Epub 2023 Apr 13.

Authors

Keisuke Obara¹, Mizuki Kaneko², Mio Yamashita², Ge Liu², Kento Yoshioka², Yoshio Tanaka²

Affiliations

¹ Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi-City, Chiba 274-8510, Japan. Electronic address: [email protected].
² Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi-City, Chiba 274-8510, Japan.

PMID: 37169476
DOI: 10.1016/j.jphs.2023.04.004

Abstract

We investigated the extracellular Ca²⁺ influx pathways involved in platelet-activating factor (PAF)-enhanced guinea pig detrusor smooth muscle (DSM) contractile activities. One micromolar PAF-enhanced DSM contractile activities were completely inhibited by extracellular Ca²⁺ removal and strongly suppressed by voltage-dependent Ca²⁺ channel (VDCC) inhibitors. PAF-enhanced DSM contractile activities remaining in the presence of verapamil (10 μM) were not inhibited by LOE-908 (30 μM, an inhibitor of receptor-operated Ca²⁺ channels (ROCCs)), but were almost completely inhibited by SKF-96365 (30 μM, an inhibitor of store-operated Ca²⁺ channels (SOCCs) and ROCCs). These results suggest that VDCCs and SOCCs are responsible for PAF-enhanced DSM contractile activities.

Keywords: Guinea pig detrusor smooth muscle; Platelet-activating factor (PAF); Voltage-dependent and store-operated Ca(2+) channels (VDCCs/SOCCs).

MeSH terms

Animals
Calcium / metabolism
Calcium Channels / metabolism
Guinea Pigs
Muscle Contraction
Muscle, Smooth* / metabolism
Platelet Activating Factor* / metabolism
Platelet Activating Factor* / pharmacology
Verapamil

Substances

Platelet Activating Factor
Calcium Channels
Verapamil
Calcium