INHIBITION OF CALCITONIN GENE-RELATED PEPTIDE BY H-CGRP(8-37) ANTAGONIZES THE CEREBRAL DILATOR RESPONSE FROM NASOCILIARY NERVE-STIMULATION IN THE CAT

The head is innervated by neurons with cell bodies in the trigeminal ganglion that contain both calcitonin gene-related peptide (CGRP) and substance P. The CGRP-containing neurons preferentially innervate the cerebral vessels and when activated produce both an increase in blood flow and local release of CGRP. In this study, the CGRP antagonist h-CGRP(8-37) was examined for its ability to interfere with trigeminal-evoked cerebral vasodilator reponses in the alpha-chloralose anaesthetised cat. Nasociliary nerve stimulation produced a characteristic frequency-dependent increase in cerebral cortical blood flow with a mean maximum of 35+/-7% at 20 Hz. Following administration of h-CGRP(8-37), this response was reduced by half with a general shift to the right of the frequency-response curve. These data further support the view that CGRP is an important transmitter agent in the trigeminovascular system that is responsible for a great part of the vasodilator capacity of trigeminal neurons.