Inhibitory Mechanism of Papaverine on Carbachol-Induced Contraction in Bovine Trachea

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  • Kaneda Takeharu
    Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University
  • Takeuchi Yukako
    Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University
  • Matsui Hirozumi
    Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University
  • Shimizu Kazumasa
    Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University
  • Urakawa Norimoto
    Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University
  • Nakajyo Shinjiro
    Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University

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Abstract

We have demonstrated that the relaxing mechanism of papaverine in phasic muscles such as ileum, urinary bladder, and uterus is different from tonic muscles such as aorta. In this study, we examined the inhibitory mechanism of papaverine on carbachol (CCh)-induced contraction in the bovine trachea. Papaverine inhibited muscle contraction and increase in [Ca2+]i level induced by CCh. Papaverine increased cAMP content but not cGMP content. Papaverine did not affect CCh-induced oxidized flavoproteins fluorescence or reduced pyridine nucleotides fluorescence. Papaverine (30 μM) remarkably inhibited muscle tension, but slightly decreased creatine phosphate and ATP contents. Iberiotoxin restored the inhibitions of muscle contraction and [Ca2+]i level induced by papaverine or dibutyryl-cAMP. These results suggested that the relaxing mechanism of papaverine in the bovine trachea is mainly due to increases of cAMP content by inhibiting phosphodiesterase and the mechanism is partially involved in the activation of BK channel by cAMP.<br>

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