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.
Ishikawa
M
M
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Ouchi
Y
Y
Orimo
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D016257:Fura-2; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D003994:Bucladesine; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D016257:Fura-2; D009638:Norepinephrine