title: AGAP, a new recombinant neurotoxic polypeptide, targets the voltage-gated calcium channels in rat small diameter DRG neurons.
abstract: A previous study showed that antitumor-analgesic peptide (AGAP), a novel recombinant polypeptide, which had been expressed in Escherichia coli, exhibits analgesic and antitumor effects in mice. In the present study, we investigated the underlying analgesic mechanism of AGAP. The effect of AGAP on voltage-gated calcium channels (VGCCs) was assessed in acutely isolated rat dorsal root ganglia (DRG) neurons using the whole-cell patch clamp technique. The results showed that AGAP potently inhibited VGCCs, especially high-voltage activated (HVA) calcium channels. AGAP inhibited HVA and T-type calcium currents in a dose-dependent manner, but had no significant effect on their dynamic functions in rat small-diameter DRG neurons. AGAP inhibited N- and L-type calcium currents at 78.2% and 57.3%, respectively. Thus, the present study demonstrates that AGAP affects calcium currents through the inhibition of N-, L- and T-type channels in DRG neurons, explaining the potential mechanisms of antinociception.
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
authors.forename: Xifang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China. Electronic address: lichunli_2014@126.com.
authors.forename: Chunli
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
authors.forename: Jingnan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Biochemistry, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
authors.forename: Jinghai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China. Electronic address: Chunfuw@gmail.com.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects*; D051381:Rats; D012604:Scorpion Venoms / Q000633:toxicity*
chemical_list: D020747:Calcium Channels, T-Type; D012604:Scorpion Venoms; C477804:antitumor-analgesic peptide, Buthus martensii
keywords: AGAP; Calcium channel; Dynamic function; Scorpion toxin; Whole-cell patch clamp