Abstract: AIM: To explore the effects and mechanism of κ opioid receptor and β adrenergic receptor stimulation on the expression of Cx43 gene and its protein in myocardium. METHODS: 40 male SD rats (250±20) g were randomly divided into different groups. Animals were given different agents according to experimental condition including κ opioid receptor and β adrenergic receptor agonist and antagonist. After 30 min, the left ventricular tissue was adopted for the later determination. RT-PCR was used to detect the amount of Cx43 mRNA and an immunohistochemical staining was used to detect the expression of Cx43 protein in myocardial cells. RESULTS: Compared with the control, the expression of Cx43 mRNA decreased with administration of U50,488H (a selective κ opioid receptor agonist), while increased with administration of isoproterenol, a β adrenergic receptor agonist. Meanwhile, U50,488H and propranolol, a non-specific β adrenergic receptor antagonist, inhibited the increased expression of Cx43 mRNA induced by isoproterenol(P<0.05). Accordingly, compared with control, the phosphorylated Cx43 protein was decreased with administration of isopreterenol. Meanwhile, both U50,488H and propranolol inhibited the decreased expression of phosphorylated Cx43 induced by isoproterenol. CONCLUSION: κ opioid receptor agonist U50,488H affects cardiac Cx43 expression via inhibiting β-adrenergic receptor signaling pathway.