Effect of calcitonin gene-related peptide on cytosolic free Ca2+ level in vascular smooth muscle.

The effect was investigated of calcitonin gene-related peptide (CGRP) on the cytosolic free Ca2+ level ([Ca2+]i) in rat aortic smooth muscle. The rat aortic spiral strip preparations without endothelium were treated with fura 2. The ratio of fluorescences (R340/380), an index of [Ca2+]i, emitted from smooth muscle was serially measured by a fluorescent spectrophotometer when excited by two wavelengths (340 and 380 nm). The tension of the preparations was measured simultaneously. CGRP produced cumulative decreases both in the tension and in R340/380 increased by norepinephrine. These reductions were significantly counteracted by the post-addition of CGRP-(8-37), a CGRP receptor antagonist (10(-6) M). The pretreatment with CGRP (10(-6.5) M) also significantly inhibited the norepinephrine-induced increase both in the tension and in R340/380. These effects of CGRP were significantly augmented by the pretreatment with 3-isobutyl-1-methylxanthine, and were significantly inhibited by the pretreatment with Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate. Dibutyryl cyclic AMP (10(-3.5) M) elicited the effects similar to CGRP. These results suggest that the decrease in [Ca2+]i is involved in the vasodilator action of CGRP and that the decrease in [Ca2+]i might be attributed to cyclic AMP production stimulated by CGRP.