I. Glasgow et al., RAT GASTRODUODENAL MOTILITY IN-VIVO - INVOLVEMENT OF NO AND ATP IN SPONTANEOUS MOTOR-ACTIVITY, American journal of physiology: Gastrointestinal and liver physiology, 38(5), 1998, pp. 889-896
Our studies of fasted anesthetized rats have shown that all spontaneou
s relaxations of the antrum are nitric oxide (NO) dependent. Duodenal
motility is patterned into propagating ''grouped'' motor activity inte
rposed with ''intergroup'' periods of nonpropagating motor activity; i
n the duodenum, only intergroup relaxations are NO dependent. We exami
ned the involvement of NO and ATP in spontaneous motor activities of t
he gastroduodenum in vivo: contractions and relaxations were recorded
and analyzed simultaneously from the antrum (S-1) and proximal duodenu
m (D-1) of anesthetized Sprague-Dawley rats (n = 10/group), using extr
aluminal 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 duo
denal contractions. ATP (8 mg.kg(-1).min(-1) iv) stimulated relaxation
s at S-1 and D-1 that were blocked by the P-2-purinoceptor antagonist
suramin (60 mg/kg iv). This treatment did not affect spontaneous antra
l relaxations; however, duodenal grouped relaxations were attenuated.
Desensitization to the P-2x-purinoceptor agonist alpha,beta-methylene
ATP (300 mu g/kg iv) gave results similar to suramin. In contrast, the
P-2y-purinoceptor agonist 2-methylthio-ATP (2-MeS-ATP; 360 mu g/kg iv
) evoked duodenal relaxations that were attenuated by L-NAME, and dese
nsitization to 2-MeS-ATP attenuated intergroup relaxations. Spontaneou
s relaxations of the rat antrum and duodenal intergroup relaxations ar
e NO dependent. Both gut regions relax in response to systemically adm
inistered ATP; this response is sensitive to suramin. Grouped duodenal
relaxations display functional sensitivity to suramin and P-2x-purino
ceptor desensitization, indicative of the involvement of ATP and P-2x
purinoceptors. P-2y 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 respons
es to L-NAME indicates that the pathway(s) controlling these responses
is modulated by NO.