PDE4 and PDE5 regulate cyclic nucleotide contents and relaxing effects on carbachol-induced contraction in the bovine abomasum

Abstract

The effects of various selective phosphodiesterase (PDE) inhibitors on carbachol (CCh)-induced contraction in the bovine abomasum were investigated. Various selective PDE inhibitors, vinpocetine (type 1), erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, type 2), milrinone (type 3), Ro20-1724 (type 4), vardenafil (type 5), BRL-50481 (type 7) and BAY73-6691 (type 9), inhibited CCh-induced contractions in a concentration-dependent manner. Among the PDE inhibitors, Ro20-1724 and vardenafil induced more relaxation than the other inhibitors based on the data for the IC50 or maximum relaxation. In smooth muscle of the bovine abomasum, we showed the expression of PDE4B, 4C, 4D and 5 by RT-PCR analysis. In the presence of CCh, Ro20-1724 increased the cAMP content, but not the cGMP content. By contrast, vardenafil increased the cGMP content, but not the cAMP content. These results suggest that Ro20-1724-induced relaxation was correlated with cAMP and that vardenafil-induced relaxation was correlated with cGMP in the bovine abomasum. In conclusion, PDE4 and PDE5 are the enzymes involved in regulation of the relaxation associated with cAMP and cGMP, respectively, in the bovine abomasum.

Effects of papaverine on carbachol- and high K⁺-induced contraction in the bovine abomasum

“…PDEs are currently classified into 11 families [ 3 ], and various selective PDE inhibitors have been found [ 5 ]. In our previous study, vardenafil (a selective PDE 5 inhibitor) induced relaxation in association with the increases in the cGMP content and was the most potent relaxing agent involved in inhibition of PDE5 [ 18 ]. This suggests that PDE 5 functions to hydrolyze cGMP in bovine abomasum.…”

Imidazole-induced contractions in bovine tracheal smooth muscle are not dependent on the cAMP pathway

“…It is also well known that the trachea is one of the organ, which has animal species difference for drug reaction [ 11 , 19 ]. We have continued research on the agents related to signal transduction of cAMP and cGMP in bovine and porcine smooth muscle [ 6 , 7 , 8 , 9 ].…”