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Tyrosine kinase involvement in apamin‐sensitive inhibitory responses of rat distal colon
Author(s) -
Takeuchi Tadayoshi,
Kishi Masami,
Hirayama Nobue,
Yamaji Michiru,
Ishii Toshiaki,
Nishio Hideaki,
Hata Fumiaki,
Takewaki Tadashi
Publication year - 1999
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.1469-7793.1999.177af.x
Subject(s) - apamin , endocrinology , medicine , hyperpolarization (physics) , sk channel , tyrosine kinase , biology , intracellular , pituitary adenylate cyclase activating peptide , genistein , chemistry , potassium channel , biochemistry , vasoactive intestinal peptide , neuropeptide , ion channel , signal transduction , receptor , organic chemistry , nuclear magnetic resonance spectroscopy
1 It has been suggested that pituitary adenylate cyclase activating peptide (PACAP) may be involved in the non‐adrenergic, non‐cholinergic (NANC) inhibitory response of longitudinal muscle of rat distal colon. In this study, we have investigated the intracellular mechanism of PACAP‐induced relaxation in this muscle. 2 PACAP induced an apamin‐sensitive relaxation of the longitudinal muscle. The tyrosine kinase inhibitors genistein at 10 μ m and tyrphostin 25 at 30 μ m , but not the cyclic AMP‐dependent protein kinase inhibitor R p ‐8‐bromoadenosine‐3′,5′‐cyclic monophosphorothioate at 30 μ m significantly inhibited the PACAP‐induced relaxation to 60% and 25% of control values, respectively. PACAP did not increase the cyclic AMP content of the muscle. 3 Tyrphostin 25 at 10 μ m significantly inhibited the relaxation of longitudinal muscle induced by electrical field stimulation (EFS), to 50% of control values. Apamin at 1 μ m , an antagonist of small conductance Ca 2+ ‐activated K + channels, also inhibited the relaxation, to 42% of control values. The inhibitory effects of tyrphostin 25 and apamin were not additive (44% of control values). 4 PACAP induced an apamin‐sensitive, slow hyperpolarization of the cell membrane of the muscle. Tyrphostin 25 at 3 μ m inhibited this PACAP‐induced hyperpolarization. Tyrphostin 25 at 10 μ m and genistein at 10 μ m inhibited the apamin‐sensitive inhibitory junction potentials induced by a single pulse of EFS. 5 The PACAP‐induced relaxation of longitudinal muscle occurred with a concomitant decrease in intracellular Ca 2+ levels ([Ca 2+ ] i ). Tyrphostin 25 at 10 μ m and apamin at 1 μ m abolished these PACAP‐induced responses. 6 From these findings it is suggested that the activation of tyrosine kinase is involved in PACAP‐induced relaxation of longitudinal muscle from rat distal colon, ‘upstream of’ the activation of apamin‐sensitive K + channels.