It’s important to determine whether NO is produced primarily or secondarily by another NANC neurotransmitter following vagal stimulation. Yokotani et al. recently demonstrated that optimum release of ACh and noradrenaline in reaction to vagal stimulation was observed at 10 and 5 Hz, respectively, while in the rat stomach. While reactions to higher frequencies of stimulation were only partly paid down by L NMMA, Cathepsin Inhibitor 1 The relaxation of rat fundic pieces evoked by transmural stimulation at lower frequencies was entirely abolished by L NMMA. On the other hand, trypsin only reduced relaxation caused by high frequencies of stimulation, indicating that the relaxation in the rat gastric fundus in response to low frequencies of stimulation was mediated largely by NO, although peptidergic neurotransmitter was released at higher frequencies. We have confirmed and extended these findings by plainly showing that the release of NO and VIP are frequency dependent. Within our current study, vagal excitement triggered a substantial increase of NO generation in the stomach, and maximum effect was seen Inguinal canal at 2 5 Hz. On another hand, VIP release in a reaction to vagal stimulation was greatest at 10 Hz. Grundy, Gharib Naseri & Hutson demonstrated that in the anaesthetized ferret, vagal stimulation produced two aspects of relaxation, a preliminary rapid relaxation followed closely by a slower relaxation. Similarly to our results, they also showed that administration of L NAME significantly reduced the first fast relaxation without impacting the slower relaxation, while VIP immunization only antagonized the slower relaxation in reaction to vagal stimulation. Nevertheless, the possible relationship between VIP and NO release in response to vagal stimulation still remains uncertain. We discovered that there was no interaction between your launch ofNO and VIP following vagal stimulation. It is unknown if NO is the final neurotransmitter mediating rapid phasic relaxation, or if it serves as an element that facilitates AG-1478 price the release of another NANC neurotransmitter. Previous studies show that NO can induce VIP release in the isolated myenteric plexus of the guinea pig ileum, suggesting a possible presynaptic stimulatory activity of NO on VIP release. However, in our studies, L NNA had no effect on vagally stimulated VIP release, and NO induced relaxation wasn’t antagonized by VIP antagonist in a vascularly isolated perfused rat stomach. For that reason, it does not seem that the action of NO is mediated by VIP in the rat stomach. Makhlouf demonstrated that VIP itself is capable of stimulating NO generation from isolated guinea pig gastric muscle cells devoid of neural elements. Nevertheless, within our studies, VIP induced gastric pleasure was not antagonized by L NNA.