Cholecystokinin octapeptide (CCK-8) has been shown to be a neuropeptide with potent anti-opioid activity. Previous studies have shown that central administration of nanogram dose of CCK-8 totally abolished morphine an...Cholecystokinin octapeptide (CCK-8) has been shown to be a neuropeptide with potent anti-opioid activity. Previous studies have shown that central administration of nanogram dose of CCK-8 totally abolished morphine analgesia in the rat, an effect mediated by CCK-B receptor in central nervous system. In the present study CCK-B antagonist L-365,260 was injected intracerebroventricularly (icv) to Wistar rats to see its effect on the analgesic effect induced by electroacupuncture (EA) stimulation. A marked potentiation of EA-induced analgesia was observed. The degree of potentiation depends on the frequency of EA used, with a rank order of 100 Hz > 15 Hz = 2/15 Hz>> 2Hz. In a strain of rat with acoustically evoked epileptic seizure (P77PMC rats), an extra-ordinarily strong analgesic effect was produced in response to 100 Hz EA stimulation, which was similar to that in Wistar rats pre-treat ed with L-365,260. However, L-365,260 was not effective in potentiating EA analgesia in P77PMC rats. The results suggest that (1) high frequency EA is more likely to increase the release of CCK-8 in CNS as compared to low frequency EA, and (2) P77PMC rats may have a functional defect of the central CCK neurons in the nature of either a low CCK content or a reduced rate of release of CCK-8 in the CNS.展开更多
OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METH...OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.展开更多
OBJECTIVE: To investigate the role of adrenomedullin (AM) in the development of hypoxic pulmonary hypertension (HPH), and to assess the expression of AM and adrenomedullin receptor (AMR) in the lungs of rats with HPH....OBJECTIVE: To investigate the role of adrenomedullin (AM) in the development of hypoxic pulmonary hypertension (HPH), and to assess the expression of AM and adrenomedullin receptor (AMR) in the lungs of rats with HPH. METHODS: We exposed 10 rats to normobaric hypoxic conditions for 3 weeks to establish rat model of pulmonary hypertension; and 10 other rats were used as normoxic controls. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization. The thickness of pulmonary arterioles was measured by a computerized image analyzer. We used the reverse transcription-polymerase chain reaction (RT-PCR) to assess the change of expression of AM and AMR in lung of HPH rat model. RESULTS: Compared with the control group, hypoxic rats developed remarkable pulmonary hypertension, increment in the thickness of pulmonary arterioles and right ventricular hypertrophy (P展开更多
基金This study was supported by the National Natural Science Foundation of China, and a grant from the National Institute of Drua Abuse, USA (DA 03983).
文摘Cholecystokinin octapeptide (CCK-8) has been shown to be a neuropeptide with potent anti-opioid activity. Previous studies have shown that central administration of nanogram dose of CCK-8 totally abolished morphine analgesia in the rat, an effect mediated by CCK-B receptor in central nervous system. In the present study CCK-B antagonist L-365,260 was injected intracerebroventricularly (icv) to Wistar rats to see its effect on the analgesic effect induced by electroacupuncture (EA) stimulation. A marked potentiation of EA-induced analgesia was observed. The degree of potentiation depends on the frequency of EA used, with a rank order of 100 Hz > 15 Hz = 2/15 Hz>> 2Hz. In a strain of rat with acoustically evoked epileptic seizure (P77PMC rats), an extra-ordinarily strong analgesic effect was produced in response to 100 Hz EA stimulation, which was similar to that in Wistar rats pre-treat ed with L-365,260. However, L-365,260 was not effective in potentiating EA analgesia in P77PMC rats. The results suggest that (1) high frequency EA is more likely to increase the release of CCK-8 in CNS as compared to low frequency EA, and (2) P77PMC rats may have a functional defect of the central CCK neurons in the nature of either a low CCK content or a reduced rate of release of CCK-8 in the CNS.
文摘OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.
基金ThisworkwassupportedbyagrantfromNationalNaturalScienceFoundationofChina (No 39770 339)
文摘OBJECTIVE: To investigate the role of adrenomedullin (AM) in the development of hypoxic pulmonary hypertension (HPH), and to assess the expression of AM and adrenomedullin receptor (AMR) in the lungs of rats with HPH. METHODS: We exposed 10 rats to normobaric hypoxic conditions for 3 weeks to establish rat model of pulmonary hypertension; and 10 other rats were used as normoxic controls. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization. The thickness of pulmonary arterioles was measured by a computerized image analyzer. We used the reverse transcription-polymerase chain reaction (RT-PCR) to assess the change of expression of AM and AMR in lung of HPH rat model. RESULTS: Compared with the control group, hypoxic rats developed remarkable pulmonary hypertension, increment in the thickness of pulmonary arterioles and right ventricular hypertrophy (P
