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Effect of metoclopramide and ranitidine on acetylcholine release from isolated rat stomach.
Arch Int Pharmacodyn Ther. 1988 Sep-Oct; 295:245-56.AI

Abstract

Metoclopramide and ranitidine (10(-6)-10(-4) M) enhanced the electrical field stimulation-evoked contractions of isolated rat fundus and increased the gastric emptying in conscious rats. The enhancement of the fundus contractions by metoclopramide and ranitidine was abolished by atropine, but not by yohimbine, hexamethonium, propranolol or methysergide. The electrical field stimulation-evoked [3H]outflow from rat fundus strips, which has been preincubated with [3H]choline, was reduced by tetrodotoxin (10(-6) M) or in calcium-free medium, and potentiated by 4-amino-pyridine (3 X 10(-4) M), an acetylcholine (ACh)-releasing agent. Metoclopramide and ranitidine (10(-6)-10(-4) M) did not increase the [3H]outflow from the strips, in spite of causing a significant enhancement of their contractile response. However, both agents caused an increase in the ratio of [3H]acetylcholine/[3H]choline released into the superfusate during electrical field-stimulation. In rat fundus homogenates, metoclopramide and ranitidine showed a significant cholinesterase inhibition. These results seem to cast a doubt on the generally held ACh release hypothesis for the action mechanism of metoclopramide on one hand, and suggest, on the other hand, that cholinesterase inhibition contributes to some extent to the gastrokinetic effects of metoclopramide and ranitidine.

Authors+Show Affiliations

Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Suita/Osaka, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

3245740

Citation

Yoshida, N, et al. "Effect of Metoclopramide and Ranitidine On Acetylcholine Release From Isolated Rat Stomach." Archives Internationales De Pharmacodynamie Et De Therapie, vol. 295, 1988, pp. 245-56.
Yoshida N, Karasawa T, Kadokawa T. Effect of metoclopramide and ranitidine on acetylcholine release from isolated rat stomach. Arch Int Pharmacodyn Ther. 1988;295:245-56.
Yoshida, N., Karasawa, T., & Kadokawa, T. (1988). Effect of metoclopramide and ranitidine on acetylcholine release from isolated rat stomach. Archives Internationales De Pharmacodynamie Et De Therapie, 295, 245-56.
Yoshida N, Karasawa T, Kadokawa T. Effect of Metoclopramide and Ranitidine On Acetylcholine Release From Isolated Rat Stomach. Arch Int Pharmacodyn Ther. 1988 Sep-Oct;295:245-56. PubMed PMID: 3245740.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of metoclopramide and ranitidine on acetylcholine release from isolated rat stomach. AU - Yoshida,N, AU - Karasawa,T, AU - Kadokawa,T, PY - 1988/9/1/pubmed PY - 1988/9/1/medline PY - 1988/9/1/entrez SP - 245 EP - 56 JF - Archives internationales de pharmacodynamie et de therapie JO - Arch Int Pharmacodyn Ther VL - 295 N2 - Metoclopramide and ranitidine (10(-6)-10(-4) M) enhanced the electrical field stimulation-evoked contractions of isolated rat fundus and increased the gastric emptying in conscious rats. The enhancement of the fundus contractions by metoclopramide and ranitidine was abolished by atropine, but not by yohimbine, hexamethonium, propranolol or methysergide. The electrical field stimulation-evoked [3H]outflow from rat fundus strips, which has been preincubated with [3H]choline, was reduced by tetrodotoxin (10(-6) M) or in calcium-free medium, and potentiated by 4-amino-pyridine (3 X 10(-4) M), an acetylcholine (ACh)-releasing agent. Metoclopramide and ranitidine (10(-6)-10(-4) M) did not increase the [3H]outflow from the strips, in spite of causing a significant enhancement of their contractile response. However, both agents caused an increase in the ratio of [3H]acetylcholine/[3H]choline released into the superfusate during electrical field-stimulation. In rat fundus homogenates, metoclopramide and ranitidine showed a significant cholinesterase inhibition. These results seem to cast a doubt on the generally held ACh release hypothesis for the action mechanism of metoclopramide on one hand, and suggest, on the other hand, that cholinesterase inhibition contributes to some extent to the gastrokinetic effects of metoclopramide and ranitidine. SN - 0003-9780 UR - https://www.unboundmedicine.com/medline/citation/3245740/Effect_of_metoclopramide_and_ranitidine_on_acetylcholine_release_from_isolated_rat_stomach_ DB - PRIME DP - Unbound Medicine ER -