The Effects of Peripheral mu and kappa Opioid Receptor Agonists on the Thermal Injury Induced Hyperalgesia in the Rat / 대한마취과학회지

BACKGROUND: Previous reports have described that the local administration of opioid receptor agonist can attenuate the nociceptive responses induced by a variety of inflammatory states. This study evaluated the effects of mu or kappa opioid receptor agonists peripherally administered at a site of injury on the state of thermal hyperalgesia induced by mild burn injury. METHODS: Thermal injury was induced after briefly anesthetizing with halothane, by applying the left hindpaw to a hot plate (52.5 degree C) for 45 seconds. Paw withdrawal latency of the hindpaw was determined using an underglass thermal stimulus, which allowed the response latency of the injured paw to be obtained. In this work, the mu receptor agonist, morphine (10, 30, 100 microgram), or the kappa receptor agonist, U50,488H (10, 30, 100 microgram), was administered respectively at the injured site on the right hindpaw in rats. To compare the systemic effects of the drug, the same drug was administered at the normal left hindpaw site with mild burn injury. Naloxone (40 microgram/kg) was administered at the injured site or at the normal site to determine the reversibility of the opioid used. RESULTS: Mild burn injury produced thermal hyperalgesia manifested as reduced paw withdrawal latency. Administration of either morphine (10, 30, 100 microgram) or U50,488H (10, 30, 100 microgram) at the injured site attenuated hyperalgesia in a dose-dependent manner. But the administration of drugs at the normal site had no effect on hyperalgesia at the injured site. In addition, naloxone had the effect of morphine and U50,488H reversed significantly. CONCLUSIONS: These results suggest that peripheral mu or kappa opioid receptor administration at an injured site may play an important role in the hyperalgesia induced by mild burn injury.

Inhibitory effects of κ-opioid receptor stimulation on ne-induced cardiac hypertrophy of the cultured myocardial cells / 中国药理学通报

AIM: To study the effects of κ-opioid receptor activation on the cardiac hypertrophy, cultured cardiomyocytes were to used study the inhibitory effects of U58,488H on cellular volume and norepinephrine(NE)-induced hypertrophy in the presence or absence of norbinaltorphimine(nor-BNI). METHODS: The protein content was assayed with Lowry's method. The cardiomyocytes' volumes was measured by an eyepiece graticule of inverted microscope. The contracting frequency of cultured myocytes was counted by the inverted microscope. RESULTS: A κ-opioid receptor agonist U50, 488H at (0.1 ∼ 10 μmol·L-1) inhibited the protein content of cultured myocardial cells in normal serum medium in a dose-dependent manner. The inhibitory effects of U50,488H were completely blocked by pretreatment with nor-BNI, a specific κ-opioid receptor antagonist at 1 μmol·L-1. U50,488H (0.1 ∼ 10 μmol·L-1) also inhibited NE-induced cellular hypertrophy in low serum medium, which also were abolished by nor-BNI (1 μmol· L-1). CONCLUSIONS: U50,488H inhibited NE-induced hypertrophy. The inhibitory effects of U50,488H are involved in mediating the action of NE-induced cardiac hypertrophy.

Anti-arrhythmic effects of U50,488H involving the inhibition of Na~+ current in ischemia/reperfusion rat heart / 中国药理学通报

Aim To investigate the effects of U50,488H(a selective ?-opioid receptor agonist)on ventricular arrhythmias induced by myocardial ischemia and reperfusion in rats and to elucidate their mechanisms.Methods The contents of CK(creatine phosphokinase)and LDH(lactate dehydrogenase)were measured; The isolated heart was perfused using langendorff equipment. Heart rate(HR), arterial blood pressure(ABP), left ventricular pressure (LVP), cardiac function (?dp/dtmax), rate of ventricular tachycardia(VT)and ventricular fibrillation(VF)were examined in rats in vitro. The incidence of ventricular arrhythmias and arrhythmia score were also determined; The change of sodium currents (INa) induced by U50,488H was detected by whole-cell recording mode using patch clamp.Results ① In comparison with I/R group, the contents of CK、LDH in plasma of rats in U50,488H+I/R group were significantly lowered(P

Inhibitory effects of ?-opioid receptor stimulation on NE-induced cardiac hypertrophy of the cultured myocardial cells / 中国药理学通报

AIM To study the effects of ?-opioid receptor activation on the cardiac hypertrophy, cultured cardiomyocytes were to used study the inhibitory effects of U58,488H on cellular volume and norepinephrine(NE)-induced hypertrophy in the presence or absence of norbinaltorphimine(nor-BNI). METHODS The protein content was assayed with Lowry's method. The cardiomyocytes'volumes was measured by an eyepiece graticule of inverted microscope. The contracting frequency of cultured myocytes was counted by the inverted microscope. RESULTS A ?-opioid receptor agonist U50,488H at (0.1～10 ?mol?L -1 ) inhibited the protein content of cultured myocardial cells in normal serum medium in a dose-dependent manner. The inhibitory effects of U50,488H were completely blocked by pretreatment with nor-BNI, a specific ?-opioid receptor antagonist at 1 ?mol?L -1 . U50,488H (0.1～10 ?mol?L -1 ) also inhibited NE-induced cellular hypertrophy in low serum medium, which also were abolished by nor-BNI(1 ?mol?L -1 ). CONCLUSIONS U50,488H inhibited NE-induced hypertrophy. The inhibitory effects of U50,488H are involved in mediating the action of NE-induced cardiac hypertrophy.