Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Pharmacological Mechanism of Action of GS283 and GS386 on Human Platelet and Pig Coronary Artery

관상동맥이완과 혈소판응집에 대한 GS283과 GS386의 약리작용기전에 관한 연구

  • CHANG, Ki Churl (Department of Pharmacology, College of Medicine, Cardiovascular Research Institute, Gyeongsang National University) ;
  • LEE, Hoi Young (Department of Pharmacology, College of Medicine, Cardiovascular Research Institute, Gyeongsang National University) ;
  • LEE, Goun Woo (Department of Pharmacology, College of Medicine, Cardiovascular Research Institute, Gyeongsang National University) ;
  • KOO, Eui Bon (Department of Pharmacology, College of Medicine, Cardiovascular Research Institute, Gyeongsang National University) ;
  • KANG, Young Jin (Department of Pharmacology, College of Medicine, Cardiovascular Research Institute, Gyeongsang National University) ;
  • LEE, Young Soo (Department of Pharmacology, College of Medicine, Cardiovascular Research Institute, Gyeongsang National University)
  • 장기철 (경상대학교 의과대학 약리학 교실, 심혈관연구소) ;
  • 이회영 (경상대학교 의과대학 약리학 교실, 심혈관연구소) ;
  • 이균우 (경상대학교 의과대학 약리학 교실, 심혈관연구소) ;
  • 구의본 (경상대학교 의과대학 약리학 교실, 심혈관연구소) ;
  • 강영진 (경상대학교 의과대학 약리학 교실, 심혈관연구소) ;
  • 이영수 (경상대학교 의과대학 약리학 교실, 심혈관연구소)
  • Published : 1997.09.01
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Abstract

Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

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