DOI QR코드

DOI QR Code

Suppressive Impact of Ginsenoside-Rg2 on Catecholamine Secretion from the Rat Adrenal Medulla

  • Ha, Kang-Su (Department of Psychiatry, College of Medicine, Chosun University) ;
  • Kim, Ki-Hwan (Division of Hematology/Medical Oncology, Department of Internal Medicine, Seoul National University Boramae Medical Center) ;
  • Lim, Hyo-Jeong (Department of Internal Medicine (Division of Pulmonary and Critical Care Medicine), Veterans Health Service Medical Center) ;
  • Ki, Young-Jae (Department of Internal Medicine (Division of Cardiology), College of Medicine, Chosun University) ;
  • Koh, Young-Youp (Department of Internal Medicine (Division of Cardiology), College of Medicine, Chosun University) ;
  • Lim, Dong-Yoon (Department of Pharmacology, College of Medicine, Chosun University)
  • Received : 2021.01.12
  • Accepted : 2021.05.31
  • Published : 2021.06.30

Abstract

This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K+, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and Nω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na+ and Ca2+ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca2+ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT1-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.

Keywords

Acknowledgement

The present study was supported by grants from the Clinical Medicine Research Institute at Chosun University Hospital (2015).

References

  1. Na, S. Y.; Kim, K. H.; Choi, M. S.; Ha, K. S.; Lim, D. Y. Korean J. Physiol. Pharmacol. 2016, 20, 629-639. https://doi.org/10.4196/kjpp.2016.20.6.629
  2. Lim, D. Y.; Park, K. B.; Kim, K. H.; Lee, K. S.; Moon, J. K.; Kim, Y. H. Korean Biochem. J. 1987, 20, 230-238.
  3. Lim, D. Y.; Park, K. B.; Kim, K. H.; Choi, C. H.; Bae, J. W.; Kim, M. W. Korean J. Pharmacol. 1988, 24, 31-42.
  4. Lim, D. Y.; Choi, C. H.; Kim, C. D.; Kim, K. H.; Kim, S. B.; Lee, B. J.; Chung, M. H. Arch. Pharm. Res. 1989, 12, 166-175. https://doi.org/10.1007/BF02855549
  5. Lim, H. J.; Le e , H. Y.; Lim, D. Y. Korean J. Physiol. Pharmacol. 2014, 18, 431-439. https://doi.org/10.4196/kjpp.2014.18.5.431
  6. Hong, S. P.; Chi, H.; Cho, S. H.; Lee, Y. K.; Woo, S. C.; Kim, I. S.; Oh, S. H.; Yang, W. H.; Lim, D. Y. Korean J. Hypert. 1999, 5, 159-168.
  7. Jang, S. J.; Lim, H. J.; Lim, D. Y. J. Ginseng Res. 2011, 35, 176-190. https://doi.org/10.5142/jgr.2011.35.2.176
  8. Kudo, K.; Akasaka, Y.; Miyate, Y.; Takahashi, E.; Tachikawa, E.; Kashimoto, T. J. Med. Pharm. Soc. Wakan-Yaku 1992, 9, 236-239.
  9. Tachikawa, E.; Kudo, K.; Kashimoto, T.; Takahashi, E. J. Pharmacol. Exp. Ther. 1995, 273, 629-636.
  10. Kudo, K.; Tachikawa, E.; Kashimoto, T.; Takahashi, E. Eur. J. Pharmacol. 1998, 341, 139-144. https://doi.org/10.1016/S0014-2999(97)01350-2
  11. Tachikawa, E.; Kudo, K.; Nunokawa, M.; Kashimoto, T.; Takahashi, E.; Kitagawa, S. Biochem. Pharmacol. 2001, 62, 943-951. https://doi.org/10.1016/S0006-2952(01)00743-2
  12. Je on, B. H.; Kim, C. S.; Kim, H. S.; Park, J. B.; Nam, K. Y.; Chang, S. J. Acta Pharmacol. Sin. 2000, 21, 1095-1100.
  13. Kim, N. D.; Kim, E. M.; Kang, K. W.; Cho, M. K.; Choi, S. Y.; Kim, S. G. Br. J. Pharmacol. 2003, 140, 661-670. https://doi.org/10.1038/sj.bjp.0705490
  14. Han, K.; Shin, I. C.; Choi, K. J.; Yun, Y. P.; Hong, J. T.; Oh, K. W. Nitric Oxide 2005, 12, 159-162. https://doi.org/10.1016/j.niox.2005.02.001
  15. Kim, N. D.; Kang, S. Y.; Schini. V. B. Gen. Pharmacol. 1994, 25, 1071-1077. https://doi.org/10.1016/0306-3623(94)90121-X
  16. Kim, N. D.; Kang, S. Y.; Park, J. H.; Schini-Kerth, V. B. Eur. J. Pharmacol. 1999, 367, 41-49. https://doi.org/10.1016/S0014-2999(98)00898-X
  17. Kang, S. Y.; Schini-Kerth, V. B.; Kim, N. D. Life Sci. 1995, 56, 1577-1586. https://doi.org/10.1016/0024-3205(95)00124-O
  18. Wakade, A. R. J. Physiol. 1981, 313, 463-480. https://doi.org/10.1113/jphysiol.1981.sp013676
  19. Anton, A. H.; Sayre, D. F. J. Pharmacol. Exp. Ther. 1962, 138, 360-375.
  20. McVeigh, G. E.; Hamilton, P.; Wilson, M.; Hanratty, C. G.; Leahey, W. J.; Devine, A. B. Morgan, D. G.; Dixon, L. J.; McGrath, L. T. Circulation 2002, 106, 208-213. https://doi.org/10.1161/01.CIR.0000021600.84149.78
  21. Tallarida, R. J.; Murray, R. B. Manual of pharmacologic calculation with computer programs: 2nd Ed; Speringer-Verlag: New York, 1987, p 132.
  22. Hammer, R.; Giachetti, A. Life Sci. 1982, 31, 2991-2998. https://doi.org/10.1016/0024-3205(82)90066-2
  23. Hano, T.; Mizukoshi, M.; Baba, A.; Nakamura, N.; Nishio, I. Blood Press Suppl. 1994, 5, 105-108.
  24. Garcia, A. G.; Sala, F.; Reig, J. A.; Viniegra, S.; Frias, J.; Fonteriz, R.; Gandia, L. Nature 1984, 309, 69-71. https://doi.org/10.1038/309069a0
  25. Lim, D. Y.; Kim, C. D.; Ahn, K. W. Arch. Pharm. Res. 1992, 15, 115-125. https://doi.org/10.1007/BF02974085
  26. Goeger, D. E.; Riley, R. T. Biochem. Pharmacol. 1989, 38, 3995-4003. https://doi.org/10.1016/0006-2952(89)90679-5
  27. Seidler, N. W.; Jona, I.; Vegh, N.; Martonosi, A. J. Biol. Chem. 1989, 264, 17816-17823. https://doi.org/10.1016/S0021-9258(19)84646-X
  28. Wada, Y.; Satoh, K.; Taira, N. Arch. Pharmacol. 1985a, 328, 382-387. https://doi.org/10.1007/BF00692905
  29. Kim, J. H.; Le e , J. H.; Paik, S. H.; Kim, J. H.; Chi, Y. H. Arch. Pharm. Res. 2012, 35, 1123-1126. https://doi.org/10.1007/s12272-012-0700-z
  30. Torres, M.; Ceballos, G.; Rubio, R. J. Neurochem. 1994, 63, 988-996. https://doi.org/10.1046/j.1471-4159.1994.63030988.x
  31. Uchiyama, Y.; Morita, K.; Kitayama, S.; Suemitsu, T.; Minami, N.; Miyasako, T.; Dohi, T. Jpn. J. Pharmacol. 1994, 65, 73-77. https://doi.org/10.1016/S0021-5198(19)35797-X
  32. O'Sullivan, A. J.; Burgoyne, R. D. J. Neurochem. 1990, 54, 1805-1808. https://doi.org/10.1111/j.1471-4159.1990.tb01238.x
  33. Breslow, M. J.; Tobin, J. R.; Bredt, D. S.; Ferris, C. D.; Snyder, S. H.; Traystman, R. J. Eur. J. Pharmacol. 1992, 210, 105-106. https://doi.org/10.1016/0014-2999(92)90659-R
  34. Breslow, M. J.; Tobin, J. R.; Bredt, D. S.; Ferris, C. D.; Snyder, S. H.; Traystman. R. J. Am. J. Physiol. 1993, 264, H464-H469.
  35. Lim, D. Y.; Hwang, D. H. Korean J. Pharmacol. 1991, 27, 53-67.
  36. Schramm, M.; Thomas, G.; Towart, R.; Franckowiak, G. Nature. 1983, 303, 535-537. https://doi.org/10.1038/303535a0
  37. Fisher, S. K.; Holz, R. W.; Agranoff, B. W. J. Neurochem. 1981, 37, 491-487. https://doi.org/10.1111/j.1471-4159.1981.tb00482.x
  38. Yanagihara, N.; Isosaki, M.; Ohuchi, T.; Oka, M. F.E.B.S. Lett. 1979, 105, 296-298. https://doi.org/10.1016/0014-5793(79)80633-X
  39. Wakade, A. R.; Wakade, T. D. Neuroscience. 1983, 10, 973-978. https://doi.org/10.1016/0306-4522(83)90235-X
  40. Kilpatrick, D. L.; Slepetis, R. J.; Kirshner, N. J. Neurochem. 1981, 36, 1245-1255. https://doi.org/10.1111/j.1471-4159.1981.tb01724.x
  41. Kilpatrick, D. L.; Slepetis, R.; Corcoran, J. J.; Kirshner, N. J. Neurochem. 1982, 38, 427-435. https://doi.org/10.1111/j.1471-4159.1982.tb08647.x
  42. Knight, D. E.; Kesteven, N. T. Proc. R. Soc. Lond. B. Biol. Sci. 1983, 218, 177-199. https://doi.org/10.1098/rspb.1983.0033
  43. Wada, A.; Takara, H.; Izumi, F.; Kobayashi, H.; Yanagihara, N. Neuroscience 1985, 15, 283-292. https://doi.org/10.1016/0306-4522(85)90135-6
  44. Kidokoro, Y.; Ritchie, A. K. J. Physiol. 1980, 307, 199-216. https://doi.org/10.1113/jphysiol.1980.sp013431
  45. Burgoyne, R. D. Biochim. Biophys. Acta. 1984, 779, 201-216. https://doi.org/10.1016/0304-4157(84)90009-1
  46. Uyama, Y.; Imaizumi, Y.; Watanabe, M. Br. J. Pharmacol. 1992, 106, 208-214. https://doi.org/10.1111/j.1476-5381.1992.tb14316.x
  47. Cheek, T. R.; O'Sullivan, A. J.; Moreton, R. B.; Berridge, M. J.; Burgoyne, R. D. F.E.B.S. Lett. 1989, 247, 429-434. https://doi.org/10.1016/0014-5793(89)81385-7
  48. Challis, R. A.; Jones, J. A.; Owen, P. J.; Boarder, M. R. J. Neurochem. 1991, 56, 1083-1086. https://doi.org/10.1111/j.1471-4159.1991.tb02033.x
  49. Azizi, M.; Guyene, T. T.; Chatellier, G.; Wargon, M.; Menard, J. Hypertension 1997, 29, 634-640. https://doi.org/10.1161/01.HYP.29.2.634