Aim: 

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an inborn error of purine metabolism, known as Lesch-Nyhan diseases. We have previously reported that HPRT-deficient (HPRT^-)-mice, besides the known loss of basal ganglia dopamine (DA) system, show an impairment of the neuromuscular contractile apparatus in the gastrointestinal (GI) tract. The aim of the present study was to evaluate GI motor activity in HPRT^--mice in relation to the dopaminergic control.

Methods: 

Mechanical activity of circular muscle strips of colon from wild type and HPRT^--mice was recorded in vitro as changes in isometric tension.

Results: 

DA induced a dose-dependent reduction of the amplitude of spontaneous and neural-evoked cholinergic contraction, being less effective in HPRT^-- mice. D1 receptor antagonist, Sch-23390, was able to antagonizes the effects induced by DA in both animal preparations, whilst sulpiride, D2 receptor antagonist, had no effect. Sch-23390 increased significantly basal tone, amplitude of spontaneous contractions and the neural-evoked cholinergic response in wild type mice. In HPRT^-- mice the effect on the spontaneous activity was lost, just a slight increase in the amplitude of the neural cholinergic contraction was observed. By Western blotting analysis the expression of D1 receptors and dopamine transporter (DAT) was found reduced in HPRT^-- mice.

Conclusion: 

These results show that in colon from HPRT^-- mice there is a dysfunction in the enteric dopaminergic system.