title: Effects of various selective phosphodiesterase inhibitors on carbachol-induced contraction and cyclic nucleotide contents in the guinea pig gall bladder.
abstract: The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide contents in the guinea pig gall bladder 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), and zaprinast (type 5), inhibited CCh-induced contractions in a concentration-dependent manner. The rank order of potency for the gall bladder was Ro20-1724 > vinpocetine > EHNA > milrinone > zaprinast, which was different from that of the trachea, taenia coli, and aorta. In the presence of CCh (0.3 muM), vinpocetine, milrinone, and Ro20-1724 each increased cAMP content, but not cGMP. By contrast, zaprinast increased cGMP content, but not cAMP, and EHNA increased both cAMP and cGMP contents. These results suggest that vinpocetine-, milrinone-, and Ro20-1724-induced relaxation was correlated with cAMP, zaprinast-induced relaxation was correlated with cGMP, and that EHNA-induced relaxation was correlated with cAMP and cGMP in the guinea pig gall bladder. In conclusion, the effect of PDE inhibitors in the guinea pig gall bladder was different from those in smooth muscles, such as the trachea, taenia coli, and aorta.
authors.affiliation: Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kaneda
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Watanabe
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shimizu
authors.forename: Norimoto
authors.initials: N
authors.lastname: Urakawa
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Nakajyo
mesh_terms: D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002217:Carbachol; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology
chemical_list: D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D014748:Vinca Alkaloids; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C013983:vinpocetine; C010192:9-(2-hydroxy-3-nonyl)adenine; D002217:Carbachol; D000242:Cyclic AMP; C011145:zaprinast; D006152:Cyclic GMP; D000225:Adenine; D020105:Milrinone