1. The role of cannabinoid (CB) receptors in the regulation of gastric acid secretion was investigated in the rat by means of functional experiments and by immunohistochemistry. 2. In anaesthetized rats with lumen-perfused stomach, the non selective CB-receptor agonist WIN 55,212-2 (0.30 - 4.00 micromol kg(-1), i.v.) and the selective CB(1)-receptor agonist HU-210 (0.03 - 1.50 micromol kg(-1), i.v.), dose-dependently decreased the acid secretion induced by both pentagastrin (30 nmol kg(-1) h(-1)) and 2-deoxy-D-glucose (1.25 mmol kg(-1), i.v.). By contrast, neither WIN 55,212-2 (1 - 4 micromol kg(-1), i.v.) nor HU-210 (0.03 - 1.50 micromol kg(-1), i.v.) did modify histamine-induced acid secretion (20 micromol kg(-1) h(-1)). The selective CB(2)-receptor agonist JWH-015 (3 - 10 micromol kg(-1), i.v.) was ineffective. 3. The gastric antisecretory effects of WIN 55,212-2 and HU-210 on pentagastrin-induced acid secretion were prevented by the selective CB(1)-receptor antagonist SR141716A (0.65 micromol kg(-1), i.v.) and unaffected by the selective CB(2)-receptor antagonist SR144528 (0.65 - 2 micromol kg(-1), i.v.). 4. Bilateral cervical vagotomy and ganglionic blockade with hexamethonium (10 mg kg(-1), i.v., followed by continuous infusion of 10 mg kg(-1) h(-1)) significantly reduced, but not abolished, the maximal inhibitory effect of HU-210 (0.3 micromol kg(-1), i.v.) on pentagastrin-induced acid secretion; by contrast, pretreatment with atropine (1 mg kg(-1), i.v.) did not modify the antisecretory effect of HU-210. 5. Immunoreactivity to the CB(1) receptor was co-localized with that of the cholinergic marker choline acetyltransferase in neural elements innervating smooth muscle, mucosa and submucosal blood vessels of rat stomach fundus, corpus and antrum. In contrast, CB(2) receptor-like immunoreactivity was not observed. 6. These results indicate that gastric antisecretory effects of cannabinoids in the rat are mediated by suppression of vagal drive to the stomach through activation of CB(1) receptors, located on pre- and postganglionic cholinergic pathways. However, the ineffectiveness of atropine in reducing the effect of HU-210 suggests that the release of non cholinergic excitatory neurotransmitters may be regulated by CB(1) receptors.

/pdf/gastric-antisecretory-role-and-immunohistochemical-xz2c61unf5.pdf

Effect of pentagastrin on gastric HCl secretion and histamine content of the stomach of rats.

Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach

1. Conscious gastric-cannulated rats were given [3H]histidine and aminoguanidine by dosage procedures intended to build up fast-turnover and slow-turnover pools of tissue [3H]histamine. Acid secretion was stimulated by I.V. infusion of pentagastrin, and the [3H]histamine content of gastric juice and excretion in urine were determined at 30 min intervals.

2. The amount of [3H]histamine in gastric juice derived from either a slow-turnover or fast-turnover pool was very low in unstimulated animals, and was not altered during pentagastrin-stimulated acid secretion.

3. From a slow-turnover pool pentagastrin caused increased urinary excretion of [3H]histamine. This was abolished by gastrectomy, so that the [3H]histamine liberated by pentagastrin from this pool appears to have been derived from the stomach. Evidence was not found for the existence of a slow-turnover histamine pool in the glandular mucosa of the stomach, and the source within the stomach of this pentagastrin-liberated histamine is thus uncertain.

4. From a fast-turnover pool pentagastrin did not cause an increased urinary excretion of [3H]histamine. The amount of [3H]histamine excreted by gastrectomized rats was not different from that produced by gastric-cannulated animals. This suggests that a high proportion of urinary histamine derived from a fast-turnover pool was non-gastric in origin.

5. Differences in the time scale of [3H]histamine release and acid secretion were not found. In some experiments the urinary output of [3H]histamine was prolonged beyond the end of pentagastrin administration and gastric acid secretion. However, the overall data do not suggest that urinary histamine output and gastric acid secretion take different time courses.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1974.sp010724

Effect of pentagastrin on gastric HCl secretion and histamine content of the stomach of rats.

Citations

Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach

The release of histamine during gastric acid secretion in conscious rats.

Proceedings: Renal control of kidney growth.