GPR143, a L-DOPA receptor, 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. Mol. Pharmacol. Neurobiol., Yokohama City Univ. Grad. Sch. Med. Dept. Medical Science and Cardiorenal Medicine, Yokohama City Univ., Sch. Med.
  • 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）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

Description

<p>We previously demonstrated that L-DOPA modulated the vascular α1-adrenergic receptor through GPR143, a G-protein coupled receptor, and sensitized vasomotor tone. The purpose of this study is to clarify the involvement of GPR143, in pulmonary hypertension (PH). We generated GPR143 gene-deficient (KO) rats and comparatively studied monocrotaline (MCT) -induced PH in wild type (WT) and Gpr143-KO rats. We evaluated the interaction between L-DOPA and adrenergic α1 receptor by contractile force of rat isolated pulmonary arteries. The degree of PH was evaluated by right ventricular systolic pressure (RVSP) and right ventricular to body weight ratio (RV/BW). In isolated pulmonary arteries, L-DOPA ( 1 μM) augmented contractile response to phenylephrine, an α1 adrenergic receptor agonist. One month after injection subcutaneously with MCT (60 mg/kg), the RVSP was attenuated in Gpr143-KO rats as compared to the WT rats (49.7 +/- 1.1 mmHg and 41.1 +/- 1.4 mmHg in WT and Gpr143-KO, p&lt;0.01, N=5). Coordinately, the RV/BW was also reduced in Gpr143-KO rats compared to the WT rats (5.8 +/- 0.3 × 10-4 and 4.9 +/- 0.2 × 10-4 in WT and Gpr143-KO, p&lt;0.05, N=7). We here provide evidence that GPR143 is involved in MCT-induced PH in rats. Further studies are needed to elucidate detailed mechanisms.</p>

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