Role of tachykininergic and cholinergic pathways in modulating canine gastric tone and compliance in vivo.

Acetylcholine and tachykinins act as co-transmitters along excitatory pathways at different gut levels. Since cholinergic pathways are involved in maintaining gastric tone during fasting, our aim was to study the possible role of tachykininergic pathways in modulating canine gastric tone and compliance in vivo by using selective tachykinin receptor antagonists. In four fasting, conscious dogs, we characterized the pressure-volume relationship in the proximal stomach by using a barostat. We increased the pressure of the intragastric bag by 2 mmHg increments every 3 min, starting from a baseline value of 2 up to 12 mmHg. Drug effects were investigated by studying pressure-volume relationships before and 15 min after intravenous (i.v.) administration of SR140333, SR48968, or SR142801 (respectively, NK (1)-, NK (2)-, and NK (3)-receptor antagonist, each at the dose of 1 mg kg (-1)) or atropine (100 microg kg (-1)). Pressure-volume curves were fitted by nonlinear regression analysis. Before drug administration, the curve that best fitted the pressure-volume relationship was exponential. SR140333, SR48968 and SR142801 did not affect baseline gastric tone or the gastric pressure-volume curve at any distension level. At a distending pressure of 6 mmHg, the Delta volumes obtained after administration of SR140333, SR48968 or SR142801 vs control were 65 +/- 28, 27 +/- 26, 14 +/- 20 ml, respectively. The same was true even when all three antagonists were administered together to achieve simultaneous blockade of all three tachykinin receptor subtypes. Atropine increased baseline gastric volume (Delta volume = 237 +/- 15 ml; P< 0.01) and significantly (P< 0.0001) shifted the pressure-volume curve to the left. After atropine, a linear equation best fitted the pressure-volume curve. We conclude that tachykininergic pathways are not involved in modulating canine gastric tone and compliance during fasting, whereas cholinergic pathways play a major role not only in maintaining gastric tone, but also in modulating the compliance of the proximal stomach to a distending stimulus. Copyright 2002 Elsevier Science Ltd. All rights reserved.