title: Negatively charged 2- and 10-microm particles activate vanilloid receptors, increase cAMP, and induce cytokine release.
abstract: Exposure to airborne pollutants, such as particulate matter (PM), is associated with increased mortality and morbidity. Indirect evidence suggested that PM-induced responses could be initiated by the activation of proton-gated receptors, including vanilloid receptors (VRs) and acid-sensitive ion channels (e.g. ASICS). We tested this hypothesis by characterizing the effects of 10- and 2-microm polystyrene carboxylate-modified particles (PC(10) and PC(2)) on HEK 293 cells expressing VR1 receptors, rat trigeminal ganglion (TG) neurons, and BEAS-2B airway epithelial cells. Zeta potential measurements revealed that these particles are negatively charged, meaning that when they adhere to a membrane they can lower the surface pH and activate proton-gated receptors. Both types of PCs induced currents and/or elevated intracellular Ca(2+) in cells that were capsaicin sensitive (CS). In about 70% of CS neurons, 10 microM capsazepine (CPZ), a VR antagonist, blocked PC-induced responses. In TG neurons in which VRs were blocked or desensitized, PCs induced an amiloride-inhibitable inward current having the characteristics of ASIC-mediated currents. Incubation of TG neurons with either capsaicin or PCs produced a CPZ-sensitive increase in cyclic AMP and cytokine (IL-6) release. In summary, we provide unequivocal evidence demonstrating that negatively charged PCs could activate VR1 and other proton-gated receptors. These data suggest that pharmacological manipulation of such receptors could prevent the physiological actions of PMs.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. agopyan@neuro.duke.edu
authors.forename: N
authors.initials: N
authors.lastname: Agopyan
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.forename: S A
authors.initials: SA
authors.lastname: Simon
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology
chemical_list: D000393:Air Pollutants; D015850:Interleukin-6; D011955:Receptors, Drug; D000242:Cyclic AMP; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium