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Mup4  -  major urinary protein 4

Rattus norvegicus

 
 
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Disease relevance of Mup4

  • Previous data indicated that the significant increase in plasma concentrations and the resultant AUCT values of both M2 and M4 in SHRs at 16 weeks of age were due to the hypertension state itself, and not to any hereditary characteristics of the SHRs [1].
 

High impact information on Mup4

  • The M2/M4 subtype-preferring antagonists tripitramine, methoctramine and AF-DX 116 were more potent in facilitating the evoked [3H]ACh release than in inhibiting the contractile response [2].
  • The site of hydroxylation of M1, M2, M3, and M5 was demonstrated to be at C-6beta position by incubating estr-4-en-6beta-ol-3,17-dione (M4), which is the direct 6beta-hydroxylated metabolite of norandrostenedione [3].
  • SK1899 was well absorbed, and the major metabolites detected in plasma and urine were penciclovir, the active antiviral compound, and 6-deoxypenciclovir (M4) in both species [4].
  • These data indicate that introduction of an isopropoxy carbonate group into one of the two hydroxyl groups of M4 did not significantly alter the oral bioavailability of penciclovir compared with famciclovir [4].
  • The metabolites in the rat and the dog were 4-hydroxyphenylpiperazine glucuronide (M1), 1,4-dihydroxyphenyl glucuronide (M2), 1,4-dihydroxyphenyl sulfate (M3) and phenylpiperazine (M4) [5].
 

Biological context of Mup4

  • The tissue distribution, and biliary and urinary excretion of four metabolites (M1-M4) of a new anthracycline antineoplastic agent (DA-125) were compared after single and multiple (7 consecutive days) intravenous (i.v.) administration to rats [6].
 

Anatomical context of Mup4

  • The data suggest that 7 consecutive days of i.v. administration of DA-125 (4 mg/kg) to rats does not lead to considerable accumulation of M1-M4 in the tissues, except in the bone marrow and thymus [6].
 

Associations of Mup4 with chemical compounds

  • Following the administration of RA-d10 to rats and dogs, oxygenated metabolites on the piperidine ring, such as M-3 and M-4, were isolated and their analysis indicated the unexpected loss of three or four deuterium atoms from the ring [7].
  • The two carboxylic acid metabolites were also conjugated with taurine (M4 and M5) [8].
  • M3 and M4 were below the detection limit in 24-h bile after both single and multiple administrations of DA-125 [6].
  • Adriamycin was metabolized to adriamycinol by the cytoplasmic aldo-keto reductase and adriamycin and adriamycinol were further metabolized to their deglycosylated aglycones, M3 and M4, respectively, by cytochrome P450 [9].
  • Aglycone daidzein (M3) and other three metabolites, 3',4',7-trihydroxyisoflavone (M1), 4',7-dihydroxyisoflavanone (M2) and 4',7-dihydroxyisoflavan (M4) were isolated from the urine following treatment with enzymes [10].
 

Analytical, diagnostic and therapeutic context of Mup4

References

  1. Pharmacokinetics of DA-125, a new anthracycline, after intravenous administration to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats. Yoon, E.J., Shim, H.J., Lee, J.J., Lee, S.D., Kim, W.B., Yang, J., Lee, M.G. Drug Metab. Dispos. (1997) [Pubmed]
  2. M4 muscarinic autoreceptor-mediated inhibition of -3H-acetylcholine release in the rat isolated urinary bladder. D'Agostino, G., Barbieri, A., Chiossa, E., Tonini, M. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  3. Discovery, biosynthesis, and structure elucidation of new metabolites of norandrostenedione using in vitro systems. Lévesque, J.F., Gaudreault, M., Aubin, Y., Chauret, N. Steroids (2005) [Pubmed]
  4. Pharmacokinetic studies of 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyl-oxybut-1-yl)purine, an oral prodrug for the antiviral agent penciclovir. Choi, W.S., Im, G.J., Kim, D.K., Kim, T.K., Jung, I., Kim, T.S., Lee, S.J., Lee, N., Kim, Y.W., Kim, J.S., Chang, K. Drug Metab. Dispos. (2001) [Pubmed]
  5. Characterization of polar urinary metabolites by ionspray tandem mass spectrometry following dansylation. Dalvie, D.K., O'Donnell, J.P. Rapid Commun. Mass Spectrom. (1998) [Pubmed]
  6. Pharmacokinetics of four metabolites of DA-125, a new anthracycline antineoplastic agent after single and multiple intravenous administration to rats. Lee, S.D., Lee, W.I., Shim, H.J., Lee, E.D., Kim, W.B., Yang, J., Kim, C.K., Lee, M.G. Journal of clinical pharmacy and therapeutics. (1996) [Pubmed]
  7. The metabolism of roxatidine acetate hydrochloride. Liberation of deuterium from the piperidine ring during hydroxylation. Honma, S., Iwamura, S., Kobayashi, R., Kawabe, Y., Shibata, K. Drug Metab. Dispos. (1987) [Pubmed]
  8. Disposition and metabolism of the hypoglycemic agent pioglitazone in rats. Krieter, P.A., Colletti, A.E., Doss, G.A., Miller, R.R. Drug Metab. Dispos. (1994) [Pubmed]
  9. Effects of dexamethasone on the pharmacokinetics of adriamycin after intravenous administration to rats. Lee, H.J., Lee, M.G. Res. Commun. Mol. Pathol. Pharmacol. (1999) [Pubmed]
  10. Urinary metabolites of daidzin orally administered in rats. Yasuda, T., Ohsawa, K. Biol. Pharm. Bull. (1998) [Pubmed]
  11. Lactate dehydrogenase activity and isoform distribution in the rat urinary bladder: effects of outlet obstruction and its removal. Polyanska, M., Arner, A., Malmquist, U., Uvelius, B. J. Urol. (1993) [Pubmed]
  12. Pharmacokinetic studies of mabuterol, a new selective beta 2-stimulant. II: Urinary metabolites of mabuterol in rats and their pharmacological effects. Horiba, M., Murai, T., Nomura, K., Yuge, T., Sanai, K., Osada, E. Arzneimittel-Forschung. (1984) [Pubmed]
 
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