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Human α‐calcitonin gene‐related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide
Author(s) -
Gray David W.,
Marshall Ian
Publication year - 1992
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.1476-5381.1992.tb14508.x
Subject(s) - calcitonin gene related peptide , endocrinology , medicine , soluble guanylyl cyclase , nitric oxide , chemistry , nitric oxide synthase , cyclase , gucy1b3 , acetylcholine , cyclic guanosine monophosphate , adenosine , guanosine , stimulation , guanylate cyclase 2c , biology , biochemistry , receptor , neuropeptide , cyclic gmp
1 The signal transduction pathway for vasorelaxation induced by human α‐calcitonin gene‐related peptide (human α‐CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10 −7 m ). 2 Vasorelaxation by human α‐CGRP was inhibited by haemogobin (10 −6 m ) and methylene blue (10 −5 m ) but was unaffected by ibuprofen (10 −5 m ). 3 Acetylcholine caused a 16 fold increase in levels of guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) with levels of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) being unaltered. Human α‐CGRP caused a 12 fold increase in levels of cyclic GMP but, in contrast to acetylcholine, evoked a 2.5 fold rise in levels of cyclic AMP. The rises in cyclic nucleotides evoked by human α‐CGRP and acetylcholine were dependent on the presence of an intact endothelium. 4 N G ‐nitro‐ l ‐arginine ( l ‐NOARG: 10 −5 m ), which inhibits nitric oxide synthase, inhibited the relaxant response to human α‐CGRP and cyclic GMP accumulation without affecting the cyclic AMP accumulation. 5 The data presented in this paper suggests that human α‐CGRP relaxes the rat thoracic aorta by releasing nitric oxide and stimulating guanylate cyclase. The stimulation of adenylate cyclase by human α‐CGRP probably precedes the activation of nitric oxide synthase but could be unrelated to the relaxant response.