Apomorphine does not decrease tissue levels of tetrahydrobiopterin in vivo

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• R(-)apomorphine is a catechol known to inhibit dihydropteridine reductase.
• Previous research suggested R(-)apomorphine might decrease catecholamine synthesis by lowering tetrahydrobiopterin levels in vivo.
• This hypothesis proposed a mechanism for R(-)apomorphine's inhibitory effects on catecholamine production.

Purpose of the Study:

• To investigate the effect of R(-)apomorphine on tetrahydrobiopterin levels in vitro and in vivo.
• To determine if R(-)apomorphine inhibits DOPA production by altering tetrahydrobiopterin levels.
• To elucidate the mechanism by which R(-)apomorphine affects catecholamine synthesis.

Main Methods:

• Experiments were conducted using PC12 cells for in vitro studies.
• In vivo studies involved analyzing rat liver and corpus striatum.
• Tetrahydrobiopterin levels and DOPA production were measured following R(-)apomorphine treatment.

Main Results:

• R(-)apomorphine treatment did not alter tetrahydrobiopterin levels in PC12 cells, rat liver, or corpus striatum.
• DOPA production was significantly reduced in PC12 cells and corpus striatum after R(-)apomorphine administration.
• The results demonstrate a dissociation between R(-)apomorphine's effect on DOPA production and tetrahydrobiopterin levels.

Conclusions:

• R(-)apomorphine inhibits DOPA production independently of changes in tetrahydrobiopterin levels.
• The mechanism of R(-)apomorphine's inhibition of catecholamine synthesis does not involve the reduction of 6(R)-L-erythro-tetrahydrobiopterin.
• This study refutes the proposed mechanism linking R(-)apomorphine's effects to tetrahydrobiopterin depletion.