Effects of cannabinoid receptor agonists on rat gastric acid secretion: Discrepancy between in vitro and in vivo data

The effects of the cannabinoid (CB)-receptor agonists WIN55,212-2 and HU-210 and the selective CB1-receptor antagonist SR141716A were tested on in vitro and in vivo acid secretion assays from the rat. In the isolated gastric fundus from immature rats, WIN55,212-2 (0.001-30 mu M), HU-210 (0.001-10 mu M), or SR141716A (0.1-10 mu M) did not change the basal acid output or acid responses to histamine, pentagastrin, or electrical field stimulation. HU-210 (0.3 mu mol/kg, intravenously) inhibited the acid response to pentagastrin in anesthetized adult, young, or immature rats with lumen-perfused stomachs; moreover, HU-210 reduced vagally induced acid secretion in adult animals, its antisecretory effect being reversed by SR141716A (0.65 mu mol/kg, intravenously). In vitro and in vivo data indicate that CB1 receptors are not located on parietal cells but, rather, on vagal pathways (possibly at preganglionic sites) supplying the gastric mucosa. The lack of effect of CB-receptor ligands in vitro cannot be ascribed to the use of immature rats, since HU-210 inhibited stimulated acid secretion in vivo, irrespective of the animal age.