Characteristics of Diprophylline-Induced Bidirectional Modulation on Rat Jejunal Contractility

Abstract

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline (20 µM) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a Ca2+ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is Ca2+ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of Ca2+, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.

Ameliorative effects of atractylodin on intestinal inflammation and co-occurring dysmotility in both constipation and diarrhea prominent rats

“…Atractylodin-induced contractile-state-dependent regulation is not an exception. Our previous studies indicated that ginsenoside Re (four-membered ring), emodin (three-membered ring), and diprophylline (two-membered ring) were also found respectively to have contractile-state-dependent regulation on rat jejunal contractility [495051]. …”

Diprophylline inhibits non‑small cell lung cancer A549 cell proliferation and migration, and promotes apoptosis, by downregulating PI3K signaling pathway

“…However, whether this effect is mediated via the MX pathway or the pathway of PDE inhibition requires further investigation. According to previous studies relating to DPL utilization in the clinic, DPL (20 µM) exerts stimulatory effects on the contractility of jejunal segments in low-contractile states, and suppressive roles in high-contractile states (24). Additionally, according to the results of the present study, 10 µM DPL was selected as the effective concentration for the majority of the experiments.…”

Fruit bromelain ameliorates rat constipation induced by loperamide

“…10 Chronic constipation is the main symptom of constipation in rats with low gastrointestinal motility compared with normal controls. 7,11 As intestinal contractility is positively correlated with the phosphorylation of the 20 kDa regulatory light chain of myosin (p-MLC 20 ), 12 the effects of fruit bromelain on the extent of p-MLC 20 and levels of myosin light chain kinase (MLCK) protein were measured using western blotting. The expression of MLCK mRNA was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR).…”