Relaxation of isolated guinea-pig trachea by apigenin, a constituent of celery, via inhibition of phosphodiesterase.

Apigenin, was reported to have vasodilatory effects by inhibiting Ca influx through both voltage- and receptor-operated calcium channels, but not by inhibiting cAMP- or cGMP-phosphodiesterases (PDEs) in rat thoracic aorta. However, apigenin was reported to inhibit PDE1, 2 and 3 in guinea-pig lung and heart. The aim of this study was to clarify that guinea-pig tracheal relaxation by apigenin whether via PDE inhibition. We isometrically recorded the tension of isolated guinea-pig tracheal segments on a polygraph. Antagonistic effects of apigenin against cumulative contractile agents or Ca induced contractions of the trachealis in normal or isotonic high-K, Ca-free Krebs solution, respectively. Effects of apigenin (15 and 30μM) on the cumulative forskolin- and nitroprusside-induced relaxations to histamine (30μM)-induced precontraction were performed. The inhibitory effects of 30-300μM apigenin and 3-isobutyl-1-methylxanthine (IBMX, positive control) on the cAMP- and cGMP-PDEs were determined. Apigenin concentration-dependently but non-competitively inhibited cumulative histamine-, carbachol- or Ca-induced contractions in normal or in the depolarized (K, 60mM) trachealis, suggesting that Ca influx through voltage-dependent calcium channels is inhibited. However, apigenin (15-30μM) parallel leftward shifted the concentration-response curves of forskolin and nitroprusside, and significantly increased the pD values of these two cyclase activators. Both apigenin and IBMX, a reference drug, concentration (10-300μM)-dependently and significantly, but non-selectively inhibited the activities of cAMP- and cGMP-PDEs in the trachealis. In conclusion, the relaxant effect of apigenin may be due to inhibition of both enzyme activities and reduction of intracellular Ca by inhibiting Ca influx in the trachealis.