Aim: 

The presence of orexins and orexin receptors have been revealed in the gastrointestinal tract. We previously observed that, in the mouse gastric fundus, orexin A (OXA) depressed the amplitude of the neurally-induced contractile responses, likely acting through nitric oxide (NO). Aim of the present study was to investigate the effects of OXA on the relaxant responses of the mouse gastric fundus.

Methods: 

Gastric longitudinal strips were prepared from the fundus region and mounted in organ baths for isometric recording. Electrical field stimulation (EFS, 4–16 Hz, 0.5 ms, 80 V for 15 s) was applied via two platinum wire rings.

Results: 

In carbachol (CCh, 1 × 10^-6M) precontracted strips, EFS elicited tetrodotoxin-sensitive fast relaxant responses that, at the highest stimulation frequency, were followed by sustained relaxations. The fast response was abolished by the NO synthesis inhibitor L-N^G-nitro arginine (L-NNA, 2 × 10^-4 M) as well as by the guanylate cyclase inhibitor ODQ (1 × 10^-6 M). OXA (3 × 10^-7 M) greatly increased the amplitude of the EFS-induced fast relaxation, in the whole range of stimulation frequency employed, without affecting the sustained one. OXA also enhanced the amplitude of the relaxant responses elicited by the ganglionic stimulating agent DMPP (1 × 10^-5 M), but had no effects on the smooth muscle relaxant responses elicited by papaverine (1 × 10^-5 M) or VIP (1 × 10^-7 M). The OX1 receptor antagonist SB-334867 (1 × 10^-5 M) reduced the amplitude of the EFS-induced fast relaxation without influencing the sustained one or the responses to papaverine and VIP.

Conclusions: 

The results indicate that, in strips from the mouse gastric fundus, OXA exerts, at the postganglionic level, a modulatory action on the nitrergic neurotransmission.