Lesch-Nyhan disease is an X-linked neurobehavioral and metabolic disorder caused by lack of hypoxanthine phosphoribosyltransferase (HPRT), a housekeeping enzyme responsible for recycling purines. The mechanisms underlying the neuropathology are not well understood, but the main neurochemical defect, in central nervous system, is linked to a dysfunction of dopaminergic pathway. In the enteric nervous system the dopaminergic nerves are a subset neurons of regulating gut motility, thus we investigated possible changes in colonic motility of HPRT ¯mice related to the dopaminergic control. We evaluated, in vitro, the mechanical activity of circular muscle strips from wild type and HPRT – mouse colon, and by Western blotting analysis, the expression of D1 receptors, dopamine transporter and tyrosine hydroxylase. Dopamine (DA) induced a reduction of the spontaneous and neural-evoked cholinergic contraction amplitude, being less effective in HPRT- mice. SCH-23390, D1 receptor antagonist, reduced DA inhibitory effects in both preparations, whilst sulpiride, D2 receptor antagonist, had no effect. SCH-23390 enhanced significantly basal tone, amplitude of spontaneous and the neural-evoked cholinergic contractions in wild type, but not in HPRT- mice, where just a slight increase of the neural cholinergic contraction amplitude was observed. Western blotting analysis showed a reduced expression of D1 receptors in HPRT- mice. Our results point out, in HPRT- mouse colon, a significant reduction in the DA effects and in the role of dopaminergic receptor that can affect colonic motility.
Mastropaolo, M., Zizzo, M., Belluardo, N., & Serio, R. (2010). DEFECTS IN DOPAMINERGIC PATHWAY AFFECT CONTRACTILITY OF COLON FROM HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE (HPRT) KNOCKOUT MICE.. Paper presented at VII Congresso annuale del Dipartimento di biologia cellulare e dello sviluppo.
Autori: | Mastropaolo, M.; Zizzo, M.; Belluardo, N.; Serio, R. |
Titolo: | DEFECTS IN DOPAMINERGIC PATHWAY AFFECT CONTRACTILITY OF COLON FROM HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE (HPRT) KNOCKOUT MICE. |
Nome del convegno: | VII Congresso annuale del Dipartimento di biologia cellulare e dello sviluppo |
Data di pubblicazione: | 2010 |
Numero di pagine: | 1 |
Citazione: | Mastropaolo, M., Zizzo, M., Belluardo, N., & Serio, R. (2010). DEFECTS IN DOPAMINERGIC PATHWAY AFFECT CONTRACTILITY OF COLON FROM HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE (HPRT) KNOCKOUT MICE.. Paper presented at VII Congresso annuale del Dipartimento di biologia cellulare e dello sviluppo. |
Tipologia: | 0 - Proceedings (TIPOLOGIA NON ATTIVA) |
Appare nelle tipologie: | 0 - Proceedings (TIPOLOGIA NON ATTIVA) |
File in questo prodotto:
File | Descrizione | Tipologia | Licenza | |
---|---|---|---|---|
zizzo 09 dip- Meeting dip09.doc | N/A | Administrator Richiedi una copia |