Effects of Various Selective Phosphodiesterase Inhibitors on Muscle Contractility in Guinea Pig Ileal Longitudinal Smooth Muscle
Takeharu Kaneda, Kazumasa Shimizu, Shinjiro Nakajyo and Norimoto Urakawa
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, 7-1 Kyonan-cho 1-chome, Musashino, Tokyo 180 Japan
Abstract: The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility in guinea pig ileal longitudinal smooth muscle were investigated. 1) 3-Isobutyl-1-methyl xanthine (IBMX) or zaprinast markedly inhibited the high K+- or carbachol (CCh)-induced contraction and increased cGMP content of the muscle strip in a concentration-dependent manner. However, these agents only slightly increased the cAMP content. Milrinone or Ro20-1724 also slightly inhibited the high K+- or CCh-induced contraction and increased the cAMP content, but did not increase cGMP. 2) In a fura2-loaded muscle, IBMX or zaprinast inhibited both contractions and the increase in intracellular Ca2+ ([Ca2+]i) level induced by high K+ or CCh, although the inhibitory effect on the [Ca2+]i level was smaller than that on muscle tension. 3) In alpha-toxin-permeabilized muscles, cGMP, IBMX or zaprinast significantly inhibited the Ca2+-induced contraction. These results suggest that IBMX and zaprinast inhibit muscle contraction in the ileal longitudinal smooth muscles mainly through an increase in cGMP and the inhibitory mechanism of IBMX or zaprinast is involved in the decreases in the [Ca2+]i level and sensitivity of contractile elements to Ca2+.
Keywords: Phosphodiesterase inhibitor, Ileal smooth muscle, Ca2+ sensitivity, Cyclic nucleotide, Cytosolic Ca2+