Human α‐calcitonin gene‐related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide

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Abstract
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 NG-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.