AIM To study relationship between effect of tetrandrine(Tet) on pleurisy and cAMP of inflammatory neutrophiles. METHODS
A model of pleurisy was established with an intrapleural injection of carrageenan (Car, 10 mg·kg -1 ) into rats. Tet was administrated by ip at 30 min befor injection of carrageenan. The exudate, neutrophils appeared in the pleural cavity of rats at 8 h were measured with routine method and the dilution tube technique respectively. cAMP concentration,
adenyl cyclase(AC) activity,
phosphodiesterase(PDE) activity of neutrophils and cytosolic free calcium concentration(
i) in neutrophils were determined with radioimmunoassay, indirect method, enzyme radiochemical assay and fluorescence colorimetric analysis respectively. The regulation of extracellular Ca 2+ on effect of Tet on PDE activity of neutrophils was also assessed in vitro . RESULTS Tet (10～80 mg·kg -1 ,ip) dose dependently decreased the exudate, neutrophil immigration, PDE activity and i in neutrophils, and increased cAMP concentration of neutrophils, but did not alter AC activity. A linear relationship was found between the reduction in the exudate and neutrophil immigration by Tet and the increment in cAMP concentration of neutrophils by Tet( r =0 990 or 0 992, P = 0 009 9 or 0 007 6 ). The increment in cAMP concentration was significantly associated with the inhibition of PDE activity of neutrophils by Tet( r =0 985, P = 0 014 9 ), which was related to the reduction in i in neutrophils by Tet( r =0 994, P = 0 005 7 ). Tet antagonized the increase in PDE activity of neutrophils induced by the combination of extracellular Ca 2+ and A 23187 in vitro. Furthermore, the antagonism of Tet was reversed by the increase in extracellular Ca 2+ concentration. CONCLUSION Tet increases cAMP concentration of neutrophils mainly due to inhibition of PDE activity resulted from the decrease in i in neutrophils. It may be one of the important mechanisms underlying the anti inflammatory action of Tet.