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Ins P 3 , but not novel Ca 2+ releasers, contributes to agonist‐initiated contraction in rabbit airway smooth muscle
Author(s) -
Iizuka Kunihiko,
Yoshii Akihiro,
Dobashi Kunio,
Horie Takeo,
Mori Masatomo,
Nakazawa Tsugio
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.915bg.x
Subject(s) - carbachol , contraction (grammar) , caffeine , chemistry , muscle contraction , medicine , endocrinology , inositol , acetylcholine , ryanodine receptor , biology , biochemistry , receptor
1 To examine the contributions of the putative Ca 2+ releasers, inositol 1,4,5‐trisphosphate (Ins P 3 ), cyclic ADP ribose (cADPR), and nicotinate adenine dinucleotide phosphate (NAADP), to carbachol (CCh)‐induced contraction in airway smooth muscle, we measured force development of permeabilized rabbit tracheal smooth muscle, human bronchial smooth muscle and guinea‐pig ileum longitudinal smooth muscle. 2 In the presence of 50 μ m GTP, CCh and Ins P 3 contracted α‐toxin‐permeabilized tracheal smooth muscle dose dependently; the EC 50 values for CCh and Ins P 3 were 1.84 μ m and 363 μ m , and the maximum responses (normalized to the 30 mM caffeine response) to 100 μ m CCh and to 800 μ m Ins P 3 were 206 ± 13.4 % (mean ± s.e.m.) and 84.4 ± 5.3 %, respectively. 3 However, cADPR (10‐300 μ m ), β‐NAD + (2.5 mM), FK506 (30 μ m ) and NAADP (100 μ m ) neither contracted the strip by themselves nor affected the subsequent CCh (1 μ m ) response. α‐Toxin‐permeabilized bronchial smooth muscle and ileum smooth muscle also responded to caffeine, Ins P 3 and CCh but not to cADPR. 4 Both 100 μ m 8‐amino‐cADPR, a selective cADPR antagonist, and 100 μ m thionicotinamide‐NADP, a selective NAADP antagonist, failed to inhibit the CCh response, although procaine abolished the caffeine, Ins P 3 and CCh responses in the permeabilized tracheal smooth muscle. 5 Although inhibition of the caffeine response by 30 μ m ryanodine was nearly complete, approximately 30 % of the Ins P 3 (300 μ m ) plus GTP (50 μ m ) response was retained, and the resultant response disappeared after the caffeine response was evoked in the presence of ryanodine. 6 Heparin (300 μg ml −1 ) blocked Ins P 3 (300 μ m ) and CCh (3 μ m ) responses in β‐escin‐permeabilized tracheal smooth muscle, while Ruthenium Red (100 μ m ) partially inhibited the CCh response. 7 Collectively, Ins P 3 but not cADPR or NAADP plays a key role in CCh‐initiated contraction, and Ins P 3 utilizes a single compartment of the caffeine/ryanodine‐sensitive stored Ca 2+ in airway smooth muscle.