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1 The modification of the vasodilator effect of calcitonin gene-related peptide (CGRP) by a panel of monoclonal antibodies (MAbs), which map to discrete epitopes on the CGRP molecule, was investigated in pig coronary artery rings (PCA). The preparations were pre-constricted with acetylcholine (3 x 10-7M) and concentration-response curves to CGRP (2 x 10-'0-2.56 x 10-8M) were obtained in the presence or absence of each MAb. 2 CGRP caused a concentration-dependent relaxation of PCAs which reached a maximum (98.2 ± 4.8%, n = 25) at 1.28 x 10-8M and gave an EC50 of 3.8 ± 0.8 x 10-9M. 3 Two MAbs which map to the N-terminal, CNl and CRA3, did not affect the CGRP response whilst a third, CRA5, significantly inhibited its effect. 4 The C-terminal MAb, CRA2, did not modify the CGRP response whilst, in contrast, CB3 (Cterminal) potentiated its effect. A similar augmentation of the CGRP-induced vasodilatation was seen in the presence of the middle-region MAb, CRA8. 5 These results suggest that regional specific MAbs can modify the vasodilator effect of CGRP causing either inhibition (CRA5, N-terminal) or potentiation (CB3, C-terminal; CRA8, middle region).

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