The relaxation of the pylorus is one of the most important factors for prom
oting gastric emptying. However, the role of inhibitory neurotransmitters i
n the regulation of pyloric relaxation and gastric emptying remains unclear
. In this study, we investigated the effects of NO biosynthesis inhibitor,
N-G-nitro-L-arginine methyl ester (L-NAME), and calcium dependent potassium
channel blocker, apamin, on vagal stimulation-induced pyloric relaxation a
nd gastric emptying in rats. Sodium nitroprusside (SNP), adenosine 5'-triph
osphate (ATP), vasoactive intestinal polypeptide (VIP) and pituitary adenyl
ate cyclase-activating peptide (PACAP) caused pyloric relaxations in a dose
dependent manner in vivo. Apamin (120 mu g/kg) significantly reduced ATP a
nd PACAP-induced pyloric relaxations without affecting SNP- or VIP-induced
relaxations. Vagal stimulation (10 V, 1 ms, 1-20 Hz)-induced pyloric relaxa
tion was significantly inhibited by L-NAME (10 mg/kg). The combined adminis
tration of L-NAME and apamin almost completely abolished vagal stimulation-
induced pyloric relaxation. L-NAME and apamin significantly increased spont
aneous contractions in the antrum, pylorus and duodenum. Increased motility
index by L-NAME and apamin was significantly higher in the pylorus and duo
denum, compared to that of antrum. L-NAME and apamin significantly delayed
liquid gastric emptying. These results suggest that besides NO, probably AT
P and PACAP, act as inhibitory neurotransmitters in the rat pylorus and reg
ulate gastric emptying. (C) 2000 Elsevier Science B.V. All rights reserved.