Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 379, Issue 3, pp 263–270 | Cite as

Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A

  • S. Inan
  • D. Y.-W. Lee
  • L. Y. Liu-Chen
  • A. Cowan
Original Article

Abstract

Kappa opioid receptor agonists induce water diuresis in animals and humans. We investigated the effects of s.c. nalfurafine, U50,488H, salvinorin A, and its longer-acting analog, 2-methoxymethyl-salvinorin B (MOM-sal B), on urinary output and sodium excretion over 5 h in euvolemic rats. Nalfurafine (0.005–0.02 mg/kg), U50,488H (0.1–10 mg/kg), and MOM-sal B (0.625–5 mg/kg) induced diuresis dose-dependently. Systemically (0.1–10 mg/kg) or centrally (50 μg, i.c.v.) administered salvinorin A was ineffective. 5′-Guanidinonaltrindole, a kappa receptor antagonist, inhibited nalfurafine- and MOM-sal B-induced diuresis. Nalfurafine and MOM-sal B had no effect on arginine vasopressin levels, measured at 2 h. Tolerance did not develop to the diuresis accompanying subchronic administration of nalfurafine (0.02 mg/kg). On the basis of our work, we (a) promote nalfurafine as a candidate diuretic to relieve water retention and (b) highlight salvinorin A as a kappa agonist that does not cause diuresis, probably because of its short duration of action.

Keywords

Nalfurafine U50,488H Salvinorin A 2-Methoxymethyl-salvinorin B GNTI Diuresis 

Notes

Acknowledgements

We thank Dr. Concetta Harakal for valuable comments and Drs. Ellen M. Unterwald and Shane A. Perrine for help in measuring cAMP levels. This study was supported by T32DA07237 from the National Institute on Drug Abuse.

References

  1. Ansonoff MA, Zhang J, Czyzyk T, Rothman RB, Stewart J, Xu H, Zjwiony J, Siebert DJ, Yang F, Roth BL, Pintar JE (2006) Antinociceptive and hypothermic effects of salvinorin A are abolished in a novel strain of κ-opioid receptor-1 knockout mice. J Pharmacol Exp Ther 318:641–648PubMedCrossRefGoogle Scholar
  2. Ashton N, Balment RJ, Blackburn TP (1989) Kappa-opioid-receptor agonists modulate the renal excretion of water and electrolytes in anaesthetized rats. Br J Pharmacol 99:181–185Google Scholar
  3. Béguin C, Potter DN, DiNieri JA, Munro TA, Richards MR, Paine TA, Berry L, Zhao Z, Roth BL, Xu W, Liu-Chen LY, Carlezon WA Jr, Cohen BM (2008) N-methylacetamide analog of salvinorin A: a highly potent and selective kappa-opioid agonist with oral efficacy. J Pharmacol Exp Ther 324:188–195PubMedCrossRefGoogle Scholar
  4. Bellissant E, Denolle T, Sinnassamy P, Bichet DG, Giudicelli JF, Lecoz F, Gandon JM, Allain H (1996) Systemic and regional hemodynamic and biological effects of a new kappa-opioid agonist, niravoline, in healthy volunteers. J Pharmacol Exp Ther 278:232–242PubMedGoogle Scholar
  5. Brooks DP, Valente M, Petrone G, Depalma PD, Sbacchi M, Clarke GD (1997) Comparison of the water diuretic activity of kappa receptor agonists and a vasopressin receptor antagonist in dogs. J Pharmacol Exp Ther 280:1176–1183PubMedGoogle Scholar
  6. Brown BL, Albano JDM, Ekins RP, Sgherzi AM, Tampion W (1971) A simple and sensitive saturation assay method for measurement of adenosine 3′,5′-cyclic monophosphate. Biochem J 121:561–562PubMedGoogle Scholar
  7. Butelman ER, Harris TJ, Kreek MJ (2004) The plant-derived hallucinogen, salvinorin A, produces κ-opioid agonist-like discriminative effects in rhesus monkeys. Psychopharmacology 172:220–224PubMedCrossRefGoogle Scholar
  8. Carlezon WA, Béguin C, Dinieri JA, Baumann MH, Richards MR, Todtenkopf MS, Rothman RB, Ma Z, Lee DY, Cohen BM (2006) Depressive-like effects of the κ-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. J Pharmacol Exp Ther 316:440–447PubMedCrossRefGoogle Scholar
  9. Craft RM, Ulibarri CM, Raub DJ (2000) Kappa opioid-induced diuresis in female vs. male rats. Pharmacol Biochem Behav 65:53–59PubMedCrossRefGoogle Scholar
  10. Endoh T, Matsuura H, Tajima A, Izumimoto N, Tajima C, Suzuki T, Narita M, Tseng L, Nagase H (1999) Potent antinociceptive effects of TRK-820, a novel kappa-opioid receptor agonist. Life Sci 65:1685–1694PubMedCrossRefGoogle Scholar
  11. Endoh T, Tajima A, Suzuki T, Kamei J, Narita M, Tseng L, Nagase H (2000) Characterization of the antinociceptive effects of TRK-820 in the rat. Eur J Pharmacol 387:133–140PubMedCrossRefGoogle Scholar
  12. Endoh T, Tajima A, Izumimoto N, Suzuki T, Saitoh A, Suzuki T (2001) TRK-820, a selective kappa-opioid agonist, produces potent antinociception in cynomolgus monkeys. Jpn J Pharmacol 85:282–290PubMedCrossRefGoogle Scholar
  13. Gadano A, Moreau R, Pessione F, Trombino C, Giuily N, Sinnassamy P (2000) Aquaretic effects of niravoline, a kappa-opioid agonist, in patients with cirrhosis. J Hepatol 32:38–42PubMedCrossRefGoogle Scholar
  14. Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J (2006) Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacology 6:3PubMedCrossRefGoogle Scholar
  15. Gottlieb HB, Varner KJ, Kenigs VA, Cabral AM, Kapusta DR (2005) Differential cardiovascular and renal responses produced by microinjection of the κ-opioid U-50488H [(trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide)methane sulfonate] into subregions of the paraventricular nucleus. J Pharmacol Exp Ther 312:678–685PubMedCrossRefGoogle Scholar
  16. Hammarlund MM, Odlind B, Paalzow LK (1985) Acute tolerance to furosemide diuresis in humans. Pharmacokinetic-pharmacodynamic modeling. J Pharmacol Exp Ther 233:447–453PubMedGoogle Scholar
  17. Huidobro-Toro JP, Parada S (1985) Kappa-opiates and urination: pharmacological evidence for an endogenous role of the kappa-opiate receptor in fluid and electrolyte balance. Eur J Pharmacol 107:1–10Google Scholar
  18. Inan S, Cowan A (2004) Kappa opioid agonists suppress choloroquine-induced scratching in mice. Eur J Pharmacol 502:233–237PubMedCrossRefGoogle Scholar
  19. Inan S, Cowan A (2006a) Agmatine-induced stereotyped scratching in mice is antagonized by nalfurafine, a kappa opioid agonist. Pharmacologist 48:38Google Scholar
  20. Inan S, Cowan A (2006b) Nalfurafine, a kappa opioid receptor agonist, inhibits scratching behavior secondary to cholestasis induced by chronic ethynylestradiol injections in rats. Pharmacol Biochem Behav 85:39–43PubMedCrossRefGoogle Scholar
  21. Ko MC, Willmont KJ, Lee H, Flory GS, Woods JH (2003) Ultra-long antagonism of kappa opioid agonist-induced diuresis by intracisternal nor-binaltorphimine in monkeys. Brain Res 982:38–44PubMedCrossRefGoogle Scholar
  22. Kramer HJ, Uhl W, Lanstetter B, Bäcker A (2000) Influence of asimadoline, a new κ-opioid receptor agonist, on tubular water absorbtion and vasopressin secretion in man. Br J Clin Pharmacol 50:227–235PubMedCrossRefGoogle Scholar
  23. McCurdy CR, Sufka KJ, Smith GH, Warnick JE, Nieto MJ (2006) Antinociceptive profile of salvinorin A, structurally unique kappa opioid receptor agonist. Pharmacol Biochem Behav 83:109–113PubMedCrossRefGoogle Scholar
  24. Prisinzano TE (2005) Psychopharmacology of the hallucinogenic sage Salvia divinorum. Life Sci 78:527–531PubMedCrossRefGoogle Scholar
  25. Prisinzano TE, Rothman RB (2008) Salvinorin A analogs as probes in opioid pharmacology. Chem Rev 108:1732–1743PubMedCrossRefGoogle Scholar
  26. Rathbun RC, Kattau RW, Leander JD (1983) Effects of mu- and kappa-opioid receptor agonists on urinary output in mice. Pharmacol Biochem Behav 19:863–866PubMedCrossRefGoogle Scholar
  27. Rimoy GH, Bhaskar NK, Wright DM, Rubin PC (1991) Mechanism of diuretic action of spiradoline (U-62066E)-a kappa opioid receptor agonist in human. Br J Clin Pharmacol 32:611–615PubMedGoogle Scholar
  28. Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Emsberger P, Rothman RB (2002) Salvinorin A: a potent naturally occurring nonnitrogenous κ opioid selective agonist. Proc Natl Acad Sci USA 99:11934–11939PubMedCrossRefGoogle Scholar
  29. Schmidt MS, Prisinzano TE, Tidgewell K, Harding W, Butelman ER, Kreek MJ, Murry DJ (2005) Determination of salvinorin A in body fluids by high performance liquid chromatography-atmospheric pressure chemical ionization. J Chromatogr B 818:221–225CrossRefGoogle Scholar
  30. Sheffler DJ, Roth BL (2003) Salvinorin A: the “magic mint” hallucinogen finds a molecular target in the kappa opioid receptor. Trends Pharmacol Sci 24:107–109PubMedCrossRefGoogle Scholar
  31. Slizgi GR, Ludens JH (1986) Role of ADH in ethylketocyclazocine-induced diuresis studies in the Brattleboro rat. Life Sci 38:2437–2440PubMedCrossRefGoogle Scholar
  32. Suzuki T, Izumimoto N, Takezawa Y, Fujimura M, Togashi Y, Nagase H, Tanaka T, Endoh H (2004) Effect of repeated administration of TRK-820, a kappa opioid receptor agonist, on tolerance to its antinociceptive and sedative actions. Brain Res 995:167–175PubMedCrossRefGoogle Scholar
  33. Togashi Y, Umeuchi H, Okano K, Ando N, Yoshizawa Y, Honda T, Kawamura K, Endoh T, Utsumi J, Kamei J, Tanaka T, Nagase H (2002) Antipruritic activity of the κ-opioid receptor agonist, TRK-820. Eur J Pharmacol 435:259–264PubMedCrossRefGoogle Scholar
  34. Unterwald EM, Cox BM, Kreek MJ, Cote TE, Izenwasser S (1993) Chronic repeated cocaine administration alters basal and opioid-regulated adenylyl cyclase activity. Synapse 15:33–38PubMedCrossRefGoogle Scholar
  35. VonVoigtlander PF, Lahti RA, Ludens JH (1983) U-50,488: a selective and structurally novel non-mu (kappa) opioid agonist. J Pharmacol Exp Ther 224:7–12PubMedGoogle Scholar
  36. Wakelkamp M, Alvan G, Gabrielsson J, Paintaud G (1996) Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration. Clin Pharmacol Ther 60:75–88PubMedCrossRefGoogle Scholar
  37. Wang Y, Tang K, Inan S, Siebert D, Holzbrabe U, Lee DY, Huang P, Li JG, Cowan A, Liu-Chen LY (2005) Comparison of pharmacological activities of three distinct κ ligands (salvinorin A, TRK-820 and 3FLB) on κ opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo. J Pharmacol Exp Ther 312:220–230PubMedCrossRefGoogle Scholar
  38. Wang Y, Chen Y, Xu W, Lee DYW, Ma Z, Rawls SM, Cowan A, Liu-Chen LY (2008) 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A. J Pharmacol Exp Ther 324:1073–1083PubMedCrossRefGoogle Scholar
  39. Wikström B, Gellert R, Ladefoged SD, Danda Y, Akai M, Ide K, Ogasawara M, Kawashima Y, Ueno K, Mori A, Ueno Y (2005) κ-Opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. J Am Soc Nephrol 16:3742–3747PubMedCrossRefGoogle Scholar
  40. Yamada K, Imal M, Yoshida S (1989) Mechanism of diuretic action of U-62,066E, a kappa opioid receptor agonist. Eur J Pharmacol 160:229–237PubMedCrossRefGoogle Scholar
  41. Yasuda K, Raynor K, Kong H, Breder CD, Takeda J, Reisine T, Bell GI (1993) Cloning and functional comparison of κ and δ opioid receptors from mouse brain. Proc Natl Acad Sci USA 90:6736–6740PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • S. Inan
    • 1
  • D. Y.-W. Lee
    • 2
  • L. Y. Liu-Chen
    • 1
  • A. Cowan
    • 1
  1. 1.Department of Pharmacology and Center for Substance Abuse ResearchTemple University School of MedicinePhiladelphiaUSA
  2. 2.Bio-Organic and Natural Products Laboratory, McLean HospitalHarvard Medical SchoolBelmontUSA

Personalised recommendations