Neurokinin A-Stimulated Phosphoinositide Breakdown in Rabbit Iris Sphincter Muscle.
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- Taniguchi Takashi
- Department of Neurobiology, Kyoto Pharmaceutical University
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- Ninomiya Haruaki
- Department of Pharmacology, Faculty of Medicine, Kyoto University
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- Fukunaga Reiko
- Department of Neurobiology, Kyoto Pharmaceutical University
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- Ebii Koichi
- Department of Neurobiology, Kyoto Pharmaceutical University
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- Yamamoto Masato
- Department of Neurobiology, Kyoto Pharmaceutical University
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- Fujiwara Motohatsu
- Department of Pharmacology, Faculty of Medicine, Kyoto University Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women''s University
抄録
Specific [3H]-substance P binding was saturable and of high affinity (KD = 2.5 nM) with a Bmax of 725 fmol/mg protein in the isolated rabbit iris sphincter muscle. The competition for [3H]-substance P binding was in the order of eledoisin > substance P > kassinin > neurokinin B > neurokinin A > physalaemin. In the same preparation, neurokinin A, as well as substance P induced a concentration-related accumulation of [3H]-inositol phosphates (IPs), and the maximum increase was about 200% of the control at 10-4 M. [D-Arg1, D-Trp7, 9, Leu11]-substance P (SP) and [D-Pro2, D-Trp7, 9]-SP (10-3 M) inhibited substance P or neurokinin A (10-4 M)-induced phosphatidylinositol 4, 5-bisphosphate (PIP2) hydrolysis significantly. [D-Arg1, D-Pro2, D-Trp7, 9, Leu11]-SP (10-3 M) also inhibited neurokinin A (10-4 M)-induced PIP2 hydrolysis significantly. Neurokinin A and substance P produced concentration-related contractions in normal Ca2+-containing medium. The contractile response was weaker in Ca2+-free medium, and there was no response in 0.2 mM EGTA medium. In Ca2+-free medium, the basal level of [3H]-IPs accumulation was smaller than that in normal medium, and neurokinin A and substance P significantly increased PIP2 hydrolysis. In the 0.2 mM EGTA containing medium, neurokinin A and substance P did not stimulate the PIP2 hydrolysis. These results suggest that in the rabbit iris sphincter muscle, there are tachykinin receptors linking to PIP2 hydorolysis and Ca2+ mobilization and that these mechanisms underlie the mechanism for the neurokinin A-induced contractile response, as well as the substance P-induced one.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 59 (2), 213-220, 1992
公益社団法人 日本薬理学会