PDE4 and PDE5 regulate cyclic nucleotide contents and relaxing effects on
carbachol-induced contraction in the bovine abomasum |
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Authors: | Takeharu KANEDA Yuuki KIDO Tsuyoshi TAJIMA Norimoto URAKAWA Kazumasa SHIMIZU |
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Institution: | 1)Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 7–1 Kyonan-cho 1-chome, Musashino, Tokyo 180–8602, Japan;2)School of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University, 7–1 Kyonan-cho 1-chome, Musashino, Tokyo 180–8602, Japan |
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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. |
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Keywords: | abomasum cAMP cGMP PDE inhibitor |
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