title: The differential effects of a selective kappa-opioid receptor agonist, U50488, in guinea pig heart tissues.
abstract: The differential effects of a selective kappa- (κ-) opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI), a selective κ-receptor antagonist, and pertussis toxin (PTX) abolished the negative inotropic effect of U50488. In contrast, the inhibitory effect was not affected by the pretreatment of atropine or propranolol. Even though U50488 exerted a negative inotropic effect in the left atrium, it did not affect the contractile force of the right atrium and ventricles paced at 2 Hz. Similarly, the beating rate of the spontaneously beating right atrium was also unaffected by U50488. These results indicate that the activation of κ-opioid receptors can only produce negative inotropic effect in left atria via activation of PTX-sensitive G protein in guinea pigs. The absence of negative inotropic effects in right atria and ventricles suggests that there may be a greater distribution of functional κ-opioid receptors in guinea pig left atria than in right atria and ventricles, and the distribution of the receptors may be species-specific.
authors: School of Medicine, Fu Jen Catholic University, No. 510 Zhongzheng Road, Xinzhuang District, New Taipei City 24205, Taiwan ; Big Data Research Centre, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Chi-Feng
authors: CF
authors: Hung
authors: Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Hsin-Ju
authors: 0000-0003-2760-2434
authors: HJ
authors: Li
authors: Department of Cardiology, Tainan Municipal Hospital, No. 670 Chongde Road, East District, Tainan 70173, Taiwan.
authors: Hsun-Hao
authors: HH
authors: Chang
authors: Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Gon-Ann
authors: GA
authors: Lee
authors: Department of Pharmacology, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Section 1, Zhongzheng District, Taipei 10051, Taiwan.
authors: Ming Jai
authors: MJ
authors: Su
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage*; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D011433:Propranolol / Q000008:administration & dosage; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*
chemical_list: D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D001285:Atropine; D011433:Propranolol; D019204:GTP-Binding Proteins