GPR143, a L-DOPA receptor, induced migration and proliferation of vascular smooth muscle cells is involved in monocrotaline-induced pulmonary hypertension in rats

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  • Nakano Masayuki
    Dept. Mol. Pharmacol. Neurobiol., Yokohama City Univ. Grad. Sch. Med. Dept. Medical Science and Cardiorenal Medicine, Yokohama City Univ., Sch. Med.
  • Hashimoto Tatsuo
    Dept. Crit. Care Med. and Dent., Kanagawa Dent. Univ. Grad. Sch. Dent.
  • Koga Motokazu
    Dept. Anesthesiology Crit. Care Med., Yokohama City Univ., Sch. Med.
  • Masukawa Daiki
    Dept. Mol. Pharmacol. Neurobiol., Yokohama City Univ. Grad. Sch. Med.
  • Oku Shinya
    Dept. Anesthesiology Crit. Care Med., Yokohama City Univ., Sch. Med.
  • Mizuno Yusuke
    Dept. Anesthesiology Crit. Care Med., Yokohama City Univ., Sch. Med.
  • Goto Takahisa
    Dept. Anesthesiology Crit. Care Med., Yokohama City Univ., Sch. Med.
  • Tamura Kouichi
    Dept. Medical Science and Cardiorenal Medicine, Yokohama City Univ., Sch. Med.
  • Goshima Yoshio
    Dept. Mol. Pharmacol. Neurobiol., Yokohama City Univ. Grad. Sch. Med.

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Other Title
  • L-DOPA受容体（GPR143）による血管平滑筋細胞の遊走と増殖はラットにおけるモノクロタリン誘発性肺高血圧に関与する

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<p>We previously demonstrated that L-DOPA modulated the vascular α1-adrenergic receptor through GPR143, a G-protein coupled receptor, and sensitized vasomotor tone. In this study, we examined a possible role of GPR143 in the pathogeneisis of pulmonary hypertension (PH). In isolated pulmonary arteries, L-DOPA (1 μM) augmented contractile response to phenylephrine, an α1 adrenergic receptor agonist. We generated GPR143 gene-deficient (Gpr143-/y) rats and comparatively studied the effect of L-DOPA. L-DOPA did not modify phenylephrine-induced response in the pulmonary arteries of Gpr143-/y rats, thereby indicating that the action of L-DOPA was mediated by GPR143. We next established monocrotaline (MCT, 60 mg/kg) -induced PH model in wild type (WT) and Gpr143-/y rats. One month after injection subcutaneously with MCT , the right ventricular systolic pressure (RVSP) was attenuated in Gpr143-/y rats as compared to the WT rats (49.7 +/- 1.1 mmHg and 41.4 +/- 1.4 mmHg in WT and Gpr143-/y, p&lt;0.05, N=5). Coordinately, the right ventricle to body weight (RV/BW) (5.4 +/- 0.2 × 10-4 and 4.7 +/- 0.1 × 10-4 in WT and Gpr143-/y, p&lt;0.01, N=12) was also reduced in Gpr143-/y rats compared to the WT rats. Furthermore, in primary cultures of pulmonary artery smooth muscle cells (PASMCs), the proliferative and migratory capacity of Gpr143-/y PASMCs after phenylephrine treatment was reduced compared to Gpr143-WT PASMCs. We here provide evidence that GPR143 may be involved in MCT-induced PH in rats by affecting the proliferative and migratory capacity of PASMCs.</p>

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