Pharmacological action of the CGRP antagonist, BIBN4096BS, on vasomotor responses in the hamster cheek pouch microcirculation

• Published in: The FASEB journal 2007, Vol.21 (6), p.A843-A843
• Main Authors: Miriel, Victor, Rivers, Richard J.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.A843

Previous work from our laboratory demonstrated a role for capsaicin‐sensitive sensory nerves in remote dilations to methacholine. In this previous study, the release of CGRP from sensory nerves was implicated based on the ability of the antagonist, CGRP8‐37, to inhibit remote dilations to methacholine. However, the concentrations of CGRP8‐37 in these experiments (30–300 μM) may inhibit neurotransmitters other than CGRP. Recently, a more specific CGRP antagonist, BIBN4096BS, was developed for clinical use. The goals of the present study are to characterize the effects of BIBN4096BS in the hamster cheek pouch microcirculation, and to determine the role of CGRP in remote dilations to capsaicin and methacholine. Dilation to 10−9 M CGRP (16.8±0.7μm to 35±2.7μm) is reversed by 10−7 BIBN4096BS within 5 minutes (18.2±1.6μm). Similarly, 10−7 BIBN4096BS pretreatment attenuates dilation to 10−9 M CGRP (control: 16±1.5 to 30.3±2.6; BIBN4096BS:18.9±1 to 20.42±1.1) while having no significant effect on baseline diameter (19.0±1 to 18.9±1). BIBN4096BS shifts the apparent EC50 to capsaicin from 31.5nM to 171nM. Microinjected capsaicin results in consistent local dilations and variable remote dilations which are inhibited by BIBN4096BS, however local and remote responses to microinjected methacholine are not affected by BIBN4096BS. The results suggest that CGRP is not the neurotransmitter involved in remote dilations to methacholine.