--- - |2 Summary Although 7,8‐dihydroxyflavone (7,8‐DHF), a synthetic agonist specific for tyrosine kinase receptor B (TrkB), has been reported to promote intestinal dynamics, its effect on gastric dynamics has not been studied as yet. In this study, we explored how 7,8‐DHF affected the carbachol (CCh)‐induced contraction of rat gastric muscle by way of measuring the contractile tension of muscular strips. We found that although 7,8‐DHF did not directly cause contraction of gastric muscle, it enhanced CCh‐induced, instead of substance P‐ or high K+‐induced, contraction. The enhancing role of 7,8‐DHF was partially blocked by ANA‐12, a blocker specific for TrkB the activation of which in the gastric strips was evidenced by its phosphorylation. Although 7,8‐DHF alone did not activate : phospholipase C (PLC)‐γ in gastric muscle, CCh did, and importantly, the combined treatment with CCh + 7,8‐DHF activated more PLC‐γ. U73122, an antagonist to PLC‐γ blocked both the CCh‐induced and the 7,8‐DHF‐enhanced/CCh‐induced contraction by ~30%. To pursue how 7,8‐DHF could augment CCh‐activated PLC‐γ phosphorylation, we first examined the effect of 7,8‐DHF on the expression of muscarinic receptors in gastric muscle and found that 7,8‐DHF specifically increased M3 but not M2 receptor expression possibly through TrkB/Akt (protein kinase B) pathway because the Akt antagonist, LY294002 significantly suppressed the 7,8‐DHF‐augmemted M3 expression and completely blocked the 7,8‐DHF‐enhanced cholinergic contraction. Supporting the result, Akt phosphorylation in the gastric muscle was enhanced by 7,8‐DHF treatment. The in vivo experiment showed that orally fed 7,8‐DHF increased gastric emptying rate. The results imply a possibility that 7,8‐DHF may be developed into a drug in the future for enhancing gastric dynamics. - Clinical and Experimental Pharmacology and Physiology, EarlyView.