ABSTRACT
We investigated the underlying mechanisms of penehyclidine hydrochloride (PHC), a novel selective anticholinergic drug on isolated rat uterus. The method of radio-immunity assay was further employed to determine cyclic adenosine mono phosphate (cAMP) levels in isolated rat uterus for comparing with selective effect on muscarinic receptor subtypes. In the assay, PHC could decrease the content of cAMP in isolated rat uterus, but the difference was not statistically significant at dose of 10 mumol/L. In conclusion, our results suggested that PHC has no or poor effect on M(2) receptor subtypes in isolated rat uterus.
Subject(s)
Cholinergic Antagonists/pharmacology , Cyclic AMP/metabolism , Quinuclidines/pharmacology , Animals , Female , In Vitro Techniques , Radioimmunoassay/methods , Rats , Receptor, Muscarinic M2/drug effects , Receptor, Muscarinic M2/metabolism , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/metabolismABSTRACT
OBJECTIVES: The aim was to characterize the effect of penehyclidine hydrochloride, which mediates the relaxation of guinea-pig isolated gastrointestinal smooth muscle, on muscarinic receptor subtypes. METHODS: Radioimmune assay was used to determine cAMP levels in isolated guinea-pig gastrointestinal smooth muscle to compare the selective effects of penehyclidine hydrochloride on muscarinic receptor subtypes. KEY FINDINGS: The results indicated that the relaxing effect of penehyclidine hydrochloride on isolated gastrointestinal smooth muscle contraction induced by acetylcholine was stronger than that of atropine (based on PA2 values). In the radioimmune assay, penehyclidine hydrochloride increased the cAMP content in isolated guinea-pig stomach smooth muscle and decreased the cAMP content in isolated guinea-pig intestinal smooth muscle, but the difference was not statistically significant at a dose of 10 mumol/l. CONCLUSIONS: The results suggest that penehyclidine hydrochloride has little or no effect on M2 receptor subtypes in guinea-pig gastrointestinal smooth muscle.
Subject(s)
Gastrointestinal Tract/drug effects , Muscle, Smooth/drug effects , Quinuclidines/pharmacology , Receptor, Muscarinic M2/physiology , Receptor, Muscarinic M3/physiology , Acetylcholine/pharmacology , Animals , Atropine/pharmacology , Cyclic AMP/biosynthesis , Dose-Response Relationship, Drug , Female , Gastrointestinal Tract/physiology , Guinea Pigs , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth/physiology , Radioligand Assay , Receptor, Muscarinic M2/antagonists & inhibitors , Receptor, Muscarinic M3/antagonists & inhibitorsABSTRACT
Erigeron multiradiatus (Lindl.) Benth is a traditional Tibetan medicine herb long used to treat various diseases related to inflammation. Our previous phytochemical studies on E. multiradiatus resulted in the isolation of scutellarin, which is a known flavone glucuronide with comprehensive pharmacological actions. In present study, we investigated the inhibition action of scutellarin on high glucose-induced vascular inflammation in human endothelial cells (ECV304 cells). Consistent with previous reports, exposure of ECV304 cells to high glucose for 24 h caused an increase of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1), and promoted cell adhesion between monocyte and ECV304 cells. However, pretreatment with scutellarin (0.1 and 1 microM) reversed these effects in a concentration-dependent manner. Scutellarin was able to inhibit the activation of NF-kappaB induced by high glucose in ECV304 cells. Furthermore, although oral administration of scutellarin (10 and 50 mg/kg) did not produce significant antihyperglycemic action, it lowered the serum MCP-1 levels significantly in alloxan-induced diabetic mice. Therefore, our results suggest that scutellarin has anti-inflammation effect that may afford some protection against hyperglycemia-induced vascular inflammatory both in vitro and in vivo.
