Calcitonin Gene-Related Peptide is Released from Capsaicin-Sensitive Nerve Fibres and Induces Vasodilatation of Human Cerebral Arteries Concomitant with Activation of Adenylyl Cyclase
Jansen, I-Olesen; Mortensen, A; Edvinsson, L; Jansen, I-Olesen, 1 Department of Experimental Vascular Research, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark; Mortensen, A, 2 Department of Neurosurgery, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark; Edvinsson, L, 3 Department of Internal Medicine, University Hospital, Lund, Sweden
Журнал:
Cephalalgia
Дата:
1996
Аннотация:
The vasomotor effects of calcilonin gene-related peptide (CGRP) analogues have been studied in circular segments of fresh human cereoral arteries obtained at neurosurgical operations using a sensitive in vitro system. Human a-CGRP, human b-CGRP, rat a-CGRP and rat b-CGRP induced strong and potent relaxation of precontracted circular vessel segments. The I<sub>max</sub> (maximum relaxant effect) to human calcitonin was low and the pD<sub>2</sub> (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human a-CGRP<sub>8-37</sub> blocked the response to human a-CGRP but not to human b-CGRP, while the putative antagonist [Tyr]CGRP<sub>28-37</sub> did not. Capsaicin (10<sup>-15</sup> - 10<sup>-8</sup> M) caused relaxation of the cerebral arteries by 22% of precontract on. Pre-treatment with 10<sup>-6</sup> M human a-CGRP<sub>8-37</sub> inhibited this relaxation. Human a-CGRP increased the cyclic AMP content of human cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human a-CGRP<sub>8-37</sub>. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.
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