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Rapid nitric oxide‐ and prostaglandin‐dependent release of calcitonin gene‐related peptide (CGRP) triggered by endotoxin in rat mesenteric arterial bed
Author(s) -
Wang Xian,
Wu Zhongxin,
Tang Yueming,
Fiscus Ronald R.,
Han Chide
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.tb15658.x
Subject(s) - calcitonin gene related peptide , nitric oxide , capsaicin , calcitonin , chemistry , ruthenium red , methylene blue , pharmacology , endocrinology , medicine , neuropeptide , calcium , biochemistry , receptor , photocatalysis , catalysis , organic chemistry
1 Our objective was to determine whether endotoxin (ETX) could directly trigger the release of calcitonin gene‐related peptide (CGRP) from perivascular sensory nerves in the isolated mesenteric arterial bed (MAB) of the rat and to determine whether nitric oxide (NO) and prostaglandins (PGs) are involved. 2 ETX caused time‐ and concentration‐dependent release of CGRP, and as much as a 17 fold increase in CGRP levels in the perfusate at 10–15 min after the administration of ETX (50 μg ml −1 ). 3 CGRP‐like immunoreactivity in the perfusate was shown to co‐elute with synthetic rat CGRP by reverse‐phase h.p.l.c. 4 Pretreatment of MAB with capsaicin or ruthenium red inhibited ETX‐induced CGRP release by 90% and 71%, respectively. ETX‐evoked CGRP release was decreased by 84% during Ca 2+ ‐free perfusion. 5 The release of CGRP evoked by ETX was enhanced by L‐arginine by 43% and inhibited by N ω ‐nitro‐L‐arginine (L‐NOARG) and methylene blue by 37% and 38%, respectively. L‐Arginine reversed the effect of L‐NOARG. 6 Indomethacin and ibuprofen also inhibited the ETX‐induced CGRP release by 34% and 44%, respectively. No additive inhibition could be found when L‐NOARG and indomethacin were concomitantly incubated. 7 The data suggest that ETX triggers the release of CGRP from capsaicin‐sensitive sensory nerves innervating blood vessels. The ETX‐induced CGRP release is dependent on extracellular Ca 2+ influx and involves a ruthenium red‐sensitive mechanism. Both NO and PGs appear to be involved in the ETX‐induced release of CGRP in the rat mesenteric arterial bed.