Effect of 5-HT1 receptor agonists on CGRP release. A, CGRP secretion as a function of sumatriptan concentration and treatment time. The effect of sumatriptan was determined on unstimulated and KCl-stimulated trigeminal neurons (cultured for 4–7 d). The amount secreted per hour was normalized to the basal rate determined before addition of buffer, 60 mmKCl, or sumatriptan (Suma) for 1 hr. Where indicated, 10 μm sumatriptan was added for 2 or 4 hr, and the amount per hour was normalized to basal. The mean basal CGRP secretion rate was 131 ± 4 pg/hr per dish. The means and the SE from at least three independent experiments are shown. *p < 0.001 when compared with control values.# p < 0.05 when compared with KCl-only values. B, The 5-HT1 receptor antagonist methiothepin blocks inhibitory effect of sumatriptan on KCl-stimulated CGRP release. The relative rates after addition of buffer (CON), KCl, KCl plus 10 μmsumatriptan (SUMA) and/or 20 μmmethiothepin (SUMA+MET) are shown. The mean basal rate was 122 ± 5 pg/hr per dish. The means and the SE from the two independent experiments are shown for each study. *p < 0.01 when compared with control values or sumatriptan values. # p < 0.05 when compared with KCl values.