Effect of muscarinic receptor blockade on canine gastric tone and compliance in vivo

Muscarinic pathways are involved in maintaining gastric tone during fasting and atropine is known to decrease gastric tone via blockade of a tonic vagal cholinergic input. Our aim was to assess the role of different muscarinic receptors in modulating canine gastric tone and compliance in vivo by using “selective” muscarinic receptor antagonists (telenzepine, AF-DX 116 and 4-DAMP for M1, M2, and M3 receptors, respectively) and the non-selective muscarinic receptor antagonist atropine. In four fasting, conscious dogs, we characterized the pressure-volume relationship in the proximal stomach by using a barostat. Drug effects were investigated by studying pressure-volume relationships before and 15 min after intravenous administration telenzepine, AF-DX 116, 4-DAMP or atropine. Pressure-volume curves were fitted by non-linear regression analysis. Before drug administration, the curve that best fitted the pressure-volume relationship was exponential. Atropine (100 μg kg−1) immediately decreased baseline gastric tone, i.e. relaxed the stomach (Δvolume at 2 mmHg = 236 ± 15 ml; P < 0.05), and significantly (P < 0.01) shifted the pressure-volume curve to the left. Telenzepine, at the lowest dose (3 μg kg−1), shifted the pressure-volume curve to the right (P < 0.01). AF-DX 116 at the lower dose (422 μg kg−1) had no effect on baseline gastric tone or the gastric pressure-volume curve, whereas the higher dose (2532 μg kg−1) significantly shifted the pressure-volume curve to the left (P < 0.01), but did not increase baseline gastric volume. Finally, 4-DAMP (13.5, 45, 135 μg kg−1) immediately decreased baseline gastric tone (Δvolume at 2 mmHg = 97 ± 29 ml, 110 ± 35 ml and 155 ± 21 ml, respectively) and significantly shifted the pressure-volume curve to the left (P < 0.01). We conclude that muscarinic pathways are involved in modulating canine gastric tone and compliance during fasting: M3 receptors seem to play a key role in excitatory pathways, whereas the shift of pressure-volume curve to the right observed with the lowest dose of telenzepine is consistent with the existence of M1 receptors on inhibitory pathways.