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

Abstract

Platelet-activating factor (PAF) not only acts as a mediator of platelet aggregation, inflammation, and allergy responses but also as a constrictor of various smooth muscle (SM) tissues, including gastrointestinal, tracheal/bronchial, and pregnancy uterine SMs. Previously, we reported that PAF induces basal tension increase (BTI) and oscillatory contraction (OC) in mouse urinary bladder SM (UBSM). In this study, we examined the Ca 2 influx pathways involved in PAF-induced BTI and OC in the mouse UBSM. PAF (10 6 M) induced BTI and OC in mouse UBSM. However, the PAF-induced BTI and OC were completely suppressed by extracellular Ca 2 removal. PAF-induced BTI and OC frequencies were markedly suppressed by voltagedependent Ca 2 channel (VDCC) inhibitors (verapamil (10 5 M), diltiazem (10 5 M), and nifedipine (10 7 M)). However, these VDCC inhibitors had a minor effect on the PAF-induced OC amplitude. The PAF-induced OC amplitude in the presence of verapamil (10 5 M) was strongly suppressed by SKF-96365 (3 10 5 M), an inhibitor of receptor-operated Ca 2 channel (ROCC) and store-operated Ca 2 channel (SOCC), but not by LOE-908 (3 10 5 M) (an inhibitor of ROCC). Overall, PAF-induced BTI and OC in mouse UBSM depend on Ca 2 influx and the main Ca 2 influx pathways in PAF-induced BTI and OC may be VDCC and SOCC. Of note, VDCC may be involved in PAF-induced BTI and OC frequency, and SOCC might be involved in PAF-induced OC amplitude. Key words platelet-activating factor (PAF), mouse urinary bladder smooth muscle, Ca 2+ influx pathway, voltage-dependent Ca 2+ channel (VDCC), store-operated Ca 2+ channel (SOCC), receptor-operated Ca 2+ channel (ROCC)

Inhibitory mechanisms of docosahexaenoic acid on carbachol-, angiotensin II-, and bradykinin-induced contractions in guinea pig gastric fundus smooth muscle

“…6 A). Note that (i) this intracellular Ca 2+ increase was unaffected by LOE-908 43 , and (ii) in a separate series of experiments, the CPA-induced intracellular Ca 2+ increase in Ca 2+ -containing medium was unaffected by verapamil plus LOE-908 (Supplementary Fig. 4 ).…”