Rat gastroduodenal motility in vivo: involvement of NO and ATP in spontaneous motor activity

Abstract

Our studies of fasted anesthetized rats have shown that all spontaneous relaxations of the antrum are nitric oxide (NO) dependent. Duodenal motility is patterned into propagating “grouped” motor activity interposed with “intergroup” periods of nonpropagating motor activity; in the duodenum, only intergroup relaxations are NO dependent. We examined the involvement of NO and ATP in spontaneous motor activities of the gastroduodenum in vivo: contractions and relaxations were recorded and analyzed simultaneously from the antrum (S1) and proximal duodenum (D1) of anesthetized Sprague-Dawley rats ( n = 10/group), using extraluminal foil strain gauges. Treatment with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10 mg/kg iv) attenuated ( P < 0.05) antral and intergroup relaxations, whereas grouped relaxations were enhanced ( P < 0.05). These effects were reversed with l-arginine (300 mg/kg iv). l-NAME also increased ( P < 0.05) the amplitude of duodenal contractions. ATP (8 mg ⋅ kg−1 ⋅ min−1iv) stimulated relaxations at S1and D1 that were blocked by the P2-purinoceptor antagonist suramin (60 mg/kg iv). This treatment did not affect spontaneous antral relaxations; however, duodenal grouped relaxations were attenuated. Desensitization to the P2x-purinoceptor agonist α,β-methylene ATP (300 μg/kg iv) gave results similar to suramin. In contrast, the P2y-purinoceptor agonist 2-methylthio-ATP (2-MeS-ATP; 360 μg/kg iv) evoked duodenal relaxations that were attenuated byl-NAME, and desensitization to 2-MeS-ATP attenuated intergroup relaxations. Spontaneous relaxations of the rat antrum and duodenal intergroup relaxations are NO dependent. Both gut regions relax in response to systemically administered ATP; this response is sensitive to suramin. Grouped duodenal relaxations display functional sensitivity to suramin and P2x- purinoceptor desensitization, indicative of the involvement of ATP and P2x purinoceptors. P2y purinoceptors must also be present; however, these occur on elements releasing NO. Although NO does not mediate grouped relaxations or duodenal contractions, the sensitivity of these responses tol-NAME indicates that the pathway(s) controlling these responses is modulated by NO.