Jpn. J. Pharmacol. 69, 75-82 (1995)

Effect of Phorbol Ester, 12-Deoxyphorbol 13-Isobutylate (DPB), on Muscle Tension and Cytosolic Ca2+ in Rat Anococcygeus 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: Effects of phorbol ester, 12-deoxyphorbol 13-isobutyrate (DPB), on muscle tension and cytosolic Ca2+ ([Ca2+]i) level was investigated in rat anococcygeus muscle in comparison with other smooth muscles. I) DPB (10-6 M) induced a large contraction and an elevation of [Ca2+]i level in rat aorta and small and rhythmic changes in tension and [Ca2+]i level in guinea pig ileum. However, DPB did not change either of the parameters in rat anococcygeus muscle. 2) DPB caused tension development without changing the [Ca2+]i level elevated by high K+, ionomycin or beta-escin in the anococcygeus muscle. 3) In the beta-escin permeabilized muscles of guinea pig ileum and urinary bladder, rabbit mesenteric artery and rat anococcygeus muscle, DPB enhanced the Ca2+-developed tension. Moreover, the enhancement was inhibit by H-7 (3 x 10-5 M). 4) DPB did not cause muscle tension to develop in the muscle of rat aorta, guinea pig ileum and rat anococcygeus muscle, pretreated with phorbol 12-myristate 13-acetate for 24 hr. In conclusion, DPB showed different contractile effects on the aorta, ileum and anococcygeus muscle, respectively. The initiation of muscle tension by DPB probably requires [Ca2+]i and the DPB-induced enhancement may be due to a Ca2+ sensitization of contractile elements in the anococcygeus muscle. Therefore, the difference between the DPB-induced response of the anococcygeus muscle and those of the other muscles seems to be due to a different Ca2+ movement caused by DPB. Moreover, it is suggested that DPB develops muscle tension by increasing [Ca2+]i and enhances it through the mediation of protein kinase C in the anococcygeus muscle as well as the other smooth muscles.

Keywords: 12-Deoxyphorbol 13-isobutylate, Anococcygeus muscle, Cytosolic Ca2+, Ca2+ sensitization, Protein kinase C

Copyright© The Japanese Pharmacological Society 1995

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