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

Abstract 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 μ g 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 Δ 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 ( Δ volume = 237 ± 15 ml; P P