Tags

Type your tag names separated by a space and hit enter

Paclitaxel and vinorelbine, evoked the release of substance P from cultured rat dorsal root ganglion cells through different PKC isoform-sensitive ion channels.
Neuropharmacology. 2009 Jul; 57(1):25-32.N

Abstract

Many patients suffer from serious adverse effects including respiratory distress and pulmonary edema during and after chemotherapy with paclitaxel or vinorelbine. These effects appear to be due to the activation of neurokinin-1 receptors. The present study investigated the influences of paclitaxel and vinorelbine on the substance P (sP) release from cultured dorsal root ganglion (DRG) cells using a radioimmunoassay. Both paclitaxel and vinorelbine evoked sP release in a dose- and time-dependent manner within 60 min at a concentration range of 0.1-10 microM. The sP release levels induced by the two drugs were attenuated by pretreatment with the protein kinase Cs (PKCs) inhibitors (bisindolylmaleimide I and Gö6976). Moreover, the paclitaxel- or vinorelbine-induced sP release was diminished in the absence of extracellular Ca2+ or the presence of LaCl3 (an extracellular Ca2+ influx blocker). A Ca2+ imaging assay further indicated that both paclitaxel and vinorelbine gradually increased the intracellular Ca2+ concentration, and these increases lasted for at least 15 min and were suppressed by Gö6976. Paclitaxel caused the membrane translocation of only PKCbeta within 10 min after stimulation, whereas vinorelbine induced the translocation of both PKCalpha and beta. The paclitaxel- and vinorelbine-induced sP release levels were separately inhibited by ruthenium red (a transient receptor potential (TRP) channel blocker) and gabapentin (an inhibitor of voltage-gated Ca2+ channels (VGCCs)). These findings suggest that paclitaxel and vinorelbine evoke the sP release from cultured DRG cells by the extracellular Ca2+ influx through TRP channels activated by PKCbeta and VGCCs activated by both PKCalpha and beta, respectively.

Authors+Show Affiliations

Department of Pharmacology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19376141

Citation

Miyano, Kanako, et al. "Paclitaxel and Vinorelbine, Evoked the Release of Substance P From Cultured Rat Dorsal Root Ganglion Cells Through Different PKC Isoform-sensitive Ion Channels." Neuropharmacology, vol. 57, no. 1, 2009, pp. 25-32.
Miyano K, Tang HB, Nakamura Y, et al. Paclitaxel and vinorelbine, evoked the release of substance P from cultured rat dorsal root ganglion cells through different PKC isoform-sensitive ion channels. Neuropharmacology. 2009;57(1):25-32.
Miyano, K., Tang, H. B., Nakamura, Y., Morioka, N., Inoue, A., & Nakata, Y. (2009). Paclitaxel and vinorelbine, evoked the release of substance P from cultured rat dorsal root ganglion cells through different PKC isoform-sensitive ion channels. Neuropharmacology, 57(1), 25-32. https://doi.org/10.1016/j.neuropharm.2009.04.001
Miyano K, et al. Paclitaxel and Vinorelbine, Evoked the Release of Substance P From Cultured Rat Dorsal Root Ganglion Cells Through Different PKC Isoform-sensitive Ion Channels. Neuropharmacology. 2009;57(1):25-32. PubMed PMID: 19376141.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paclitaxel and vinorelbine, evoked the release of substance P from cultured rat dorsal root ganglion cells through different PKC isoform-sensitive ion channels. AU - Miyano,Kanako, AU - Tang,He-Bin, AU - Nakamura,Yoki, AU - Morioka,Norimitsu, AU - Inoue,Atsuko, AU - Nakata,Yoshihiro, Y1 - 2009/04/17/ PY - 2008/12/30/received PY - 2009/03/09/revised PY - 2009/04/02/accepted PY - 2009/4/21/entrez PY - 2009/4/21/pubmed PY - 2009/10/2/medline SP - 25 EP - 32 JF - Neuropharmacology JO - Neuropharmacology VL - 57 IS - 1 N2 - Many patients suffer from serious adverse effects including respiratory distress and pulmonary edema during and after chemotherapy with paclitaxel or vinorelbine. These effects appear to be due to the activation of neurokinin-1 receptors. The present study investigated the influences of paclitaxel and vinorelbine on the substance P (sP) release from cultured dorsal root ganglion (DRG) cells using a radioimmunoassay. Both paclitaxel and vinorelbine evoked sP release in a dose- and time-dependent manner within 60 min at a concentration range of 0.1-10 microM. The sP release levels induced by the two drugs were attenuated by pretreatment with the protein kinase Cs (PKCs) inhibitors (bisindolylmaleimide I and Gö6976). Moreover, the paclitaxel- or vinorelbine-induced sP release was diminished in the absence of extracellular Ca2+ or the presence of LaCl3 (an extracellular Ca2+ influx blocker). A Ca2+ imaging assay further indicated that both paclitaxel and vinorelbine gradually increased the intracellular Ca2+ concentration, and these increases lasted for at least 15 min and were suppressed by Gö6976. Paclitaxel caused the membrane translocation of only PKCbeta within 10 min after stimulation, whereas vinorelbine induced the translocation of both PKCalpha and beta. The paclitaxel- and vinorelbine-induced sP release levels were separately inhibited by ruthenium red (a transient receptor potential (TRP) channel blocker) and gabapentin (an inhibitor of voltage-gated Ca2+ channels (VGCCs)). These findings suggest that paclitaxel and vinorelbine evoke the sP release from cultured DRG cells by the extracellular Ca2+ influx through TRP channels activated by PKCbeta and VGCCs activated by both PKCalpha and beta, respectively. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/19376141/Paclitaxel_and_vinorelbine_evoked_the_release_of_substance_P_from_cultured_rat_dorsal_root_ganglion_cells_through_different_PKC_isoform_sensitive_ion_channels_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(09)00106-3 DB - PRIME DP - Unbound Medicine ER -