An Investigation of the Antinociceptive Activity of Calcitonin Gene-Related Peptide Alone and in Combination with Morphine: Correlation to 45Ca Uptake by Synaptosomes1

A 5- or 30-mm incubation of synaptosomes with calcitonin gene-related peptide (CGRP) (1 0_6, 1 0, 1 0 M) produced increases in 45Ca uptake upon depolarization of the synaptosomes, whereas a naloxone-reversible decrease in 45Ca uptake was seen after a 1-hr incubation with CGRP. Morphine-induced (1 0_6 M) decreases in 45Ca uptake were reversed by simultaneous 5-mm incubation of synaptosomes with CGRP (1 0_6 M) and were enhanced by a 1-hr preincubation of the synaptosomes with CGRP (1 0_6 M). CGRP produced naloxone-reversible antinoci-ception in both the p-phenylquinone and hot-plate tests at 1 hr after i.C.V. administration, a time which corresponds to the peak CGRP-induced decrease in 45Ca uptake. CGRP (0.02 g through 40 g i.C.v.) failed to produce antinociception in the tail-flick test. However, 30-mm pretreatment of mice with CGRP (