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VIP‐ and PACAP‐mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: involvement of activation of charybdotoxin‐ and apamin‐sensitive K + channels
Author(s) -
Kishi Masami,
Takeuchi Tadayoshi,
Suthamnatpong Naowarat,
Ishii Toshiaki,
Nishio Hideaki,
Hata Fumiaki,
Takewaki Tadashi
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15719.x
Subject(s) - apamin , charybdotoxin , vasoactive intestinal peptide , pituitary adenylate cyclase activating peptide , endocrinology , antagonist , medicine , chemistry , sk channel , potassium channel , receptor , neuropeptide , biology , ion channel , biochemistry
1 The mediators of nonadrenergic, noncholinergic (NANC) inhibitory responses in longitudinal muscle of rat distal colon were studied. 2 An antagonist of pituitary adenylate cyclase activating peptide (PACAP) receptors, PACAP 6–38 , concentration‐dependently inhibited the rapid relaxation of the longitudinal muscle induced by electrical field stimulation (EFS), resulting in a maximal inhibition of 47% at 3 μ m . 3 PACAP 6–38 inhibited the relaxation by 75% in the presence of the vasoactive intestinal peptide (VIP) receptor antagonist, VIP 10–28 at μ m , which inhibited the relaxation by 44%. 4 An antagonist of large conductance Ca 2+ ‐activated K + channels, charybdotoxin, concentration‐dependently inhibited the rapid relaxation of the longitudinal muscle, resulting in a maximal inhibition of 58% at 100 nM. 5 An antagonist of small conductance Ca 2+ ‐activated K + channels, apamin, concentration‐dependently inhibited the relaxation (58% at 1 μ m ). 6 Treatment with both K + channel antagonists resulted in 84% inhibition of the EFS‐induced relaxation, which is comparable to the extent of inhibition induced by PACAP 6–38 plus VIP 10–28 . 7 The inhibitory effect of VIP 10–28 and of apamin, but not of charybdotoxin was additive: the same applied to PACAP 6–38 and charybdotoxin, but not apamin. 8 Exogenously added VIP (100 nM‐1 μ m ) induced a slow gradual relaxation of the longitudinal muscle. Charybdotoxin, but not apamin significantly inhibited the VIP‐induced relaxation. VIP 10–28 , but not PACAP 6–38 selectively inhibited the VIP‐induced relaxation. 9 Exogenously added PACAP (10–100 nM) also induced slow relaxation. Apamin and to a lesser extent, charybdotoxin, inhibited the PACAP‐induced relaxation. PACAP 6–38 , but not VIP 10–28 selectively inhibited the PACAP‐induced relaxation. 10 Apamin at 100 nM inhibited inhibitory junction potentials (i.j.ps) induced by a single pulse of EFS. Apamin also inhibited a rapid phase, but not a delayed phase of i.j.ps induced by two pulses at 10 Hz. VIP 10–28 did not inhibit i.j.ps induced by a single pulse, but significantly inhibited the delayed phase at two pulses. A combination of apamin and VIP 10–28 abolished the i.j.ps induced by two pulses. 11 Both VIP and PACAP induced slow hyperpolarization of the cell membrane of the longitudinal muscle. Apamin inhibited the PACAP‐, but not VIP‐induced hyperpolarization. 12 From these findings it is suggested that VIP and PACAP are involved in NANC inhibitory responses of longitudinal muscle of the rat distal colon via activation of charybdotoxin‐ and apaminsensitive K + channels, respectively.