Bromocriptine modulates P-glycoprotein function

Biochem Biophys Res Commun. 1998 Mar 17;244(2):481-8. doi: 10.1006/bbrc.1998.8289.


The multidrug resistance (MDR)-associated P-glycoprotein (P-gp) is a membrane transporter which carries, at the expense of MgATP hydrolysis, many amphiphilic molecules, such as the MDR-related cytotoxic drugs vincristine and vinblastine, and the MDR-reversing agents verapamil and progesterone. We have tested the effects on P-gp function of bromocriptine (BCT), an ergot alkaloid known as a D2 dopaminergic receptor agonist. BCT (at 4 microM) partially reverses the P-gp-mediated vincristine resistance of the Chinese hamster lung fibroblasts DC-3F/ADX, a MDR cell line. P-gp containing membrane vesicles prepared from the DC-3F/ADX cells exhibit, in the absence of any added drug, a basal MgATPase activity due to P-gp. BCT inhibits this basal ATPase activity, with a half-inhibiting concentration of 0.30 +/- 0.15 microM. BCT also inhibits the verapamil-induced P-gp ATPase stimulation competitively (Ki approximately 0.2 microM), and the progesterone-induced P-gp ATPase stimulation non-competitively (Ki approximately 0.07-0.10 microM). BCT also non-competitively inhibits the vinblastine-dependent P-gp ATPase activity within the same concentration range. Hydroxylated metabolites of BCT have different effects on P-gp ATPase, only the monohydroxylated being able to modulate both the basal and the drug-stimulated ATPase activities. In conclusion, these effects of BCT on P-gp function can be linked to a specific interaction with P-gp, probably involving inhibition of P-gp-mediated drug transport.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Biological Transport, Active
  • Bromocriptine / metabolism
  • Bromocriptine / pharmacokinetics
  • Bromocriptine / pharmacology*
  • Ca(2+) Mg(2+)-ATPase / antagonists & inhibitors
  • Cell Line, Transformed
  • Cricetinae
  • Dopamine Agonists / pharmacology
  • Drug Resistance
  • Drug Resistance, Multiple
  • Hydroxylation
  • Kinetics
  • Progesterone / pharmacology
  • Vincristine / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Dopamine Agonists
  • Bromocriptine
  • Progesterone
  • Vincristine
  • Ca(2+) Mg(2+)-ATPase