Molecular mechanism involved in the transport of a prodrug dopamine glycosyl conjugate

A. Dalpiaz, R. Filosa, P. de Caprariis, G. Conte, F. Bortolotti, C. Biondi, A. Scatturin, Puttur D Prasad, B. Pavan

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

We have previously demonstrated that dopamine conjugation to glucose allows it to induce therapeutic effects against Parkinson's disease after intravenous administration. In this paper we demonstrate that, unlike dopamine, the prodrug glu-dopamine is a transportable substrate of glucose transporters. Towards this, the effect of glucose-conjugation on the affinity and uptake of dopamine have been assessed in vitro, using human retinal pigment epithelium (HRPE) cells. Glucose transporter-mediated uptake was measured using [3H]3-O-methylglucose ([3H]3-O-MG) as the tracer. The uptake was found to be rapid and hyperbolically related to its concentrations (Kt = 7.8 ± 1.2 mM and Vmax = 54 ± 2 nmol/min mg protein). Inhibition experiments showed that dopamine was able to interact with glucose carriers only when conjugated to glucose (IC50 = 2.6 ± 0.6 mM). HPLC analysis of HRPE cell extracts showed that both dopamine and the prodrug permeate the cell, but only the uptake of the prodrug is inhibitable by glucose. This confirms that glucose transporters mediate the transport of the prodrug glu-dopamine, but not of dopamine. HRPE cells is therefore proposed as a promising model for in vitro studies involving the glucose transporter-mediated transport of drugs and their conjugates.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume336
Issue number1
DOIs
StatePublished - May 4 2007

Fingerprint

Prodrugs
Dopamine
Facilitative Glucose Transport Proteins
Retinal Pigment Epithelium
Glucose
3-O-Methylglucose
Therapeutic Uses
Cell Extracts
Intravenous Administration
Inhibitory Concentration 50
Parkinson Disease
High Pressure Liquid Chromatography
Pharmaceutical Preparations

Keywords

  • Dopamine
  • Drug targeting
  • Glucose
  • Glucose transporters
  • HRPE cells

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Dalpiaz, A., Filosa, R., de Caprariis, P., Conte, G., Bortolotti, F., Biondi, C., ... Pavan, B. (2007). Molecular mechanism involved in the transport of a prodrug dopamine glycosyl conjugate. International Journal of Pharmaceutics, 336(1), 133-139. https://doi.org/10.1016/j.ijpharm.2006.11.051

Molecular mechanism involved in the transport of a prodrug dopamine glycosyl conjugate. / Dalpiaz, A.; Filosa, R.; de Caprariis, P.; Conte, G.; Bortolotti, F.; Biondi, C.; Scatturin, A.; Prasad, Puttur D; Pavan, B.

In: International Journal of Pharmaceutics, Vol. 336, No. 1, 04.05.2007, p. 133-139.

Research output: Contribution to journalArticle

Dalpiaz, A, Filosa, R, de Caprariis, P, Conte, G, Bortolotti, F, Biondi, C, Scatturin, A, Prasad, PD & Pavan, B 2007, 'Molecular mechanism involved in the transport of a prodrug dopamine glycosyl conjugate', International Journal of Pharmaceutics, vol. 336, no. 1, pp. 133-139. https://doi.org/10.1016/j.ijpharm.2006.11.051
Dalpiaz, A. ; Filosa, R. ; de Caprariis, P. ; Conte, G. ; Bortolotti, F. ; Biondi, C. ; Scatturin, A. ; Prasad, Puttur D ; Pavan, B. / Molecular mechanism involved in the transport of a prodrug dopamine glycosyl conjugate. In: International Journal of Pharmaceutics. 2007 ; Vol. 336, No. 1. pp. 133-139.
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