Vasoactive intestinal polypeptide (VIP; over 10-13 M) inhibited the norepinephrine (NE)-induced contraction evoked from the rabbit mesenteric artery. Increased concentrations of VIP (over 10-9 M) inhibited the contractions induced by caffeine and 39 mM [K](o). However, VIP (below 10-7 M) had no effect on the membrane potential and resistance of muscle cells. In Ca-free solution, VIP (10-10 M) inhibited the NE-induced contraction, but the second application of NE after removal of VIP enlarged the amplitude of contraction over that in the control. Yet when 10-9 M VIP was applied, both the first and second contractions were consistently smaller than those observed by application of 10-10 M VIP. In Na- and Ca-free solution, repetitive applications of NE generated contractions longer than those observed in Ca-free solution. When VIP (10-10 M) was applied once (3 min), the contraction was inhibited only once during repetitive applications of NE. VIP (over 10-9 M) dose dependently inhibited the NE-induced contraction and had a long-lasting inhibition after washout of the tissue. In saponin-treated skinned muscles, VIP (10-7 M) had no effect on the Ca-induced contraction or on the Ca store sites. VIP (over 10-8 M) was about 10 times more potent than equimolar concentrations of isoproterenol in increasing the content of adenosine 3',5'-cyclic monophosphate (cAMP). These results indicate that VIP (10-10 M) selectively inhibits the Ca release activated by NE, and high concentrations (over 10-9 M) would expectedly increase the Ca extrusion from cells following increase in the levels of cAMP.
|ジャーナル||American Journal of Physiology - Heart and Circulatory Physiology|
|出版ステータス||出版済み - 1月 1 1985|
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