Vol. 299, Issue 3, 945-950, December 2001

Evidence for the Interaction between Nitric Oxide and Vasoactive Intestinal Polypeptide in the Mouse Gastric Fundus

Yusuf Ergün and Nuran Öülener

Cukurova University, Faculty of Medicine, Department of Pharmacology, Adana, Turkey

The involvement of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) in nonadrenergic noncholinergic (NANC) nerve-induced relaxation and the interaction between NO and VIP were investigated in the mouse gastric fundus. N-nitro-L-arginine (L-NOARG; 100 µM) completely inhibited the NANC relaxations induced by electrical stimulation (ES) (0.5, 1, 2, 4, and 8 Hz; 25 V; 1 ms; 15-s trains). Hemoglobin (20 µM), hydroxocobalamin (100 µM), and 1H-[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 µM) diminished ES-induced relaxations, but -chymotrypsin (10 U/ml) and VIP antiserum (1/200 dilution) had no effect on NANC relaxations. L-NOARG (100 µM) did not have any effect, whereas ODQ (10 µM) attenuated sodium nitroprusside (SNP; 100 nM)-induced relaxations. -Chymotrypsin (10 U/ml) had no effect on the response to SNP. Furthermore, -chymotrypsin (10 U/ml) abolished and VIP antiserum (1/200 dilution) diminished VIP (50 nM)-induced relaxations. L-NOARG (100 µM) caused an inhibition of VIP-induced relaxation that was reversed by L-arginine (1 mM) but not by D-arginine (1 mM). Similarly, ODQ (10 µM) inhibited the responses to VIP. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (5 µM) had no effect on these relaxations. L-NOARG (100 µM) and ODQ (10 µM) did not affect isoproterenol (10 nM)-induced relaxations. In conclusion, these results provide evidence that NO is involved in NANC nerve-induced relaxation and the participation of VIP (and related neuropeptides) cannot be excluded in causing relaxation of mouse gastric fundus muscle strips. These findings support the idea that VIP directly stimulates the production of NO by increasing NOS activity and thereby activating soluble guanylyl cyclase in smooth muscle.