Aim: 

The presence of orexins and their receptors has been revealed in the gastrointestinal tract. Aim of the present study was to investigate whether orexin A (OXA) exerts direct muscular effects on the mouse duodenum.

Methods: 

Duodenal segments were mounted in organ baths for isometric recording of the mechanical activity. Voltage dependent ionic currents were recorded in current- and voltage-clamp conditions by single microelectrode inserted in a duodenal smooth muscle cell (DSMC).

Results: 

Duodenal preparations exhibited spontaneous mechanical activity. Addition of OXA to the bath medium caused a transient, TTX- and atropine-insensitive, contraction that decayed after 1.5-2 min of contact time. Electrophysiological studies showed that all control DSMC exhibited Na⁺, Ca²⁺ and the delayed rectifier K⁺ current, I_Na, I_Ca and I_K(V). OXA enhanced the I_Na size by shifting the Boltzmann activation curve towards more negative potential, and the I_Ca and I_K(V) sizes prevalently by increasing their channel conductance. These potentiating effects were time-dependent. The consequence was that the depolarization induced by the increased of I_Ca was progressively counteracted by the hyperpolarising action of I_K(V). The effects of OXA were observed in the presence of TTX and those on I_Ca also in a TEA bath solution, Na⁺ free, with Ca²⁺ the only permeant ion.

Conclusion: 

The results indicate that OXA exerts direct excitatory effects on the mouse duodenal smooth muscle.