title: 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.
authors.affiliation: 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.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kaneda
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Kido
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tajima
authors.forename: Norimoto
authors.initials: N
authors.lastname: Urakawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000018:Abomasum / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002417:Cattle / Q000502:physiology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D002217:Carbachol; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5