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Calcitonin gene‐related peptide (CGRP)‐enhanced non‐adrenergic non‐cholinergic contraction of guinea‐pig proximal colon
Author(s) -
Kojima ShuIchi,
Shimo Yasuo
Publication year - 1995
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.1476-5381.1995.tb15038.x
Subject(s) - calcitonin gene related peptide , guanethidine , medicine , endocrinology , hexamethonium , tachykinin receptor , chemistry , tetrodotoxin , contraction (grammar) , cholinergic , stimulation , receptor , calcitonin , antagonist , substance p , neuropeptide
1 We have investigated the effect of calcitonin gene‐related peptide (CGRP) on non‐adrenergic, non‐cholinergic (NANC) excitatory transmission to the longitudinal muscle of the guinea‐pig proximal colon. 2 In the presence of atropine (0.3μ m ), guanethidine (5 μ m ), hexamethonium (100 μm) and indomethacin (3 μm), electrical field stimulation (EFS, 1 Hz, 0.3 ms for 10 s) produced tetrodotoxin‐(300 nM)‐sensitive contractions which were reduced by the combined administration of FK 888 (10 μm) and MEN 10,376 (0.3 μ m ), to block tachykinin NK i and NK 2 receptors, respectively. Thus, the EFS‐induced NANC contractions are a tachykinin‐mediated response. 3 CGRP, at concentrations higher than 0.1 nM, caused an increase in the electrically‐evoked, NANC contractions in a concentration‐dependent manner and at 10 nM produced a maximal effect (pEC 50 = 9.20±0.17, n = 6). 45 ‐Hydroxytryptamine (5‐HT, 1–100 nM) also caused an increase in the EFS‐induced NANC contractions in a concentration‐dependent manner and at 30 nM produced a maximal effect (pEC 50 = 8.06 ±0.09, n = 4), but calcitonin (10–100 nM) failed to enhance the EFS‐induced NANC responses. Moreover, a 5‐HT 4 receptor antagonist, DAU 6285 (3 μm) abolished the enhancing action of 5‐HT (30 nM). 5 The combined administration of FK 888 (10 μ m ) plus MEN 10,376 (0.3 μ m ) abolished the enhancement of EFS‐induced NANC contractions by CGRP (10 nM), but DAU 6285 (3 μ m ) had no effect on the enhancement. 6 Human CGRP 8_37 (1 μm), a CGRP 1 receptor antagonist had no effect on the submaximal enhancement of the electrically‐evoked, NANC contractions by CGRP (1 nM). 7 CGRP (30 nM) had no effect on contractions evoked by exogenous substance P (0.3‐1 nM). 8 These results indicate that in the guinea‐pig proximal colon, CGRP produced an enhancement of NANC contraction induced by EFS through prejunctional mechanisms and that the enhancement is mediated by the stimulation of non‐CGRP 1 receptors located on intramural tachykininergic neurones. Further, the possible contribution of 5‐HT to the enhancing effect of CGRP appeared to be negligible.