The mechanisms of the increase in gastric mucosal blood flow in response to DQ-2511, a new antiulcer agent

• Published in: Japanese Journal of Pharmacology Vol. 52; no. suppl-1.1; p. 274
• Main Authors: Hatanaka, Satoshi, Komada, Tohru, Ryokawa, Yuichi
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1990
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)55645-1

We have previously reported that DQ-2511 can effectively increase gastric mucosal blood flow and such property may contribute, at least in part, to its antiulcer activity in rats. In the present study, the effects of DQ-2511 on various isolated vascular smooth muscle preparations were examined in order to clarify the mechanisms by which this agent increased gastric blood flow. In the aorta, mesenteric artery and gastric artery, DQ-2511(10-100 μM) non-competitively inhibited norepinephrine(NE)-induced contraction in a concentration-dependent manner. This activity was approximately 10-fold greater than that on either serotonin- or KCl-induced contraction. In the mesenteric artery, removal of the endothelium almost completely reduced the vascular relaxation induced by acetylcholine(ACh, 1 μM), but was without effect on the vasodilation induced by DQ-2511(100 μM). The dilator responses to ACh and DQ-2511 were abolished with methylene blue(3 μM), a guanylate cyclase inhibitor, which did not affect the response to papaverine(10 μM). These findings suggest that the vasodilation by DQ-2511 is related to augmentation of intracellular cyclic GMP content, which is independent of the release of endothelium derived relaxing factor. The vasodilator activity of DQ-2511 may contribute to the increase in gastric mucosal blood flow in response to this agent.