Antagonism of metergoline on the diuretic effect of cyclazocine and U-50488 drugs with a kappa agonist activity |
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| Institution: | 1. Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada;1. Department of Radiology, St. Vincent''s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Gyeonggi-Do, South Korea;2. Department of Internal Medicine, St. Vincent''s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Gyeonggi-Do, South Korea;1. Department of Cardiology, Kameda Medical Center, Chiba, Japan;2. University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands;3. Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan;4. Department of Cardiology, St. Marianna University School of Medicine, Kawasaki, Japan;5. Department of Cardiology, Himeji Cardiovascular Center, Himeji, Japan;6. Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan;7. Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan;8. Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan;9. Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan;10. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio;11. Departments of Epidemiology & Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts;12. Department of Cardiovascular Medicine, Juntendo University, Tokyo, Japan;13. Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan |
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| Abstract: | In rats receiving a normal saline load of 2.5 ml/100 g, sc, (moderately hydrated rats), injections of the serotonin (5-HT) antagonist, metergoline (0.25 - 1 - 4 mg/kg), resulted in a dose-dependent decrease in the urine output induced by a dose of 8 mg/kg of cyclazocine (a benzomorphan derivative, mixed kappa and sigma agonist) at the 2-h time period. The antagonist effect of metergoline (1 mg/kg) on cyclazocine doses ranging from 0.25 to 8 mg/kg, was observed only at 2 mg/kg higher doses. Other 5-HT receptor blockers, methysergide, pizotifen, cyproheptadine, caused a significant degree of antagonism. In rats receiving a saline load and a water load of 5.5 ml/100 g, ip (hyperhydrated rats), metergoline (1 mg/kg) completely antagonized the diuretic effect of cyclazocine (8 mg/kg) at the 4-h and 5-h time periods. Similarly, metergoline (1 and 4 mg/kg) administered in moderately hydrated rats, markedly decreased at the 2-h time period, the urine output produced by 5 mg/kg of U-50488 (a non benzomorphan derivative, highly selective kappa agonist), and in hyperhydrated rats, completely suppressed, at the 4-h and 5-h time periods the drug-induced diuresis. Metergoline administered alone had no effect on urine output in moderately hydrated rats or in hyperhydrated rats. These results suggest the hypothesis that 5-HT may be involved in the complex mechanisms of kappa agonist-induced diuresis in rats. |
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