A model of bidirectional regulation induced by a combination of one stimulatory and one inhibitory agent on gastric smooth muscle contraction

摘要

In this paper, we proposed a model of counterbalance resulting from bidirectional regulation on gastric smooth muscle contraction in the absence of nervous and endocrine system control. To verify the propose, we suggested that a combination of one stimulatory and one inhibitory drug should produce bidirectional regulation on the contractility of gastric smooth muscle and myosin activity, depending on the contractile state of the gastric smooth muscle and myosin phosphorylation extent, regardless of the individual mechanism of drug action. We selected two stimulatory drugs, that is, hesperidin and emodin, and three inhibitory drugs, that is, berberine, synephrine, and quercetin, using them in stimulatory-inhibitory drug pair. Our assay supports the model we proposed. The common characteristics of these drug combinations demonstrate that inhibitory effect is observed when smooth muscle strip is present in a relatively high contractile state and myosin is fully phosphorylated, and that stimulatory effect is observed when smooth muscle strip is in a relatively low contractile state and myosin is partially phosphorylated. Regardless of the individual mechanism of drug action, the combination of one stimulatory and one inhibitory agent showed the characterization of counterbalance resulting from bidirectional regulation. This model implies the presence of counterbalance in cellular level maintained by bidirectional regulation in gastric smooth muscle, and the combination of one stimulatory and one inhibitory drug provides the information for the potential therapy of gastric smooth muscle contractility related disorders.