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

David W. Gray, Ian Marshall

    Research output: Contribution to journalArticle

    123 Citations (Scopus)

    Abstract

    1. The signal transduction pathway for vasorelaxation induced by human a-calcitonin gene-related peptide (human a-CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10-7 M). 2. Vasorelaxation by human a-CGRP was inhibited by haemoglobin (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 a-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 a-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 synthetase, inhibited the relaxant response to human alpha-CGRP and cyclic GMP accumulation without affecting the cyclic AMP accumulation. 5. The data presented in this paper suggests that human alpha-CGRP relaxes the rat thoracic aorta by releasing nitric oxide and stimulating guanylate cyclase. The stimulation of adenylate cyclase by human a-CGRP probably precedes the activation of nitric oxide synthase but could be unrelated to the relaxant response.

    Original languageEnglish
    Pages (from-to)691-6
    Number of pages6
    JournalBritish Journal of Pharmacology
    Volume107
    Issue number3
    DOIs
    Publication statusPublished - 1992

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