Effects of synthetic human calcitonin gene-related peptide (hCGRP) on Ca2+ mobilization in crude synaptosomes prepared from rat spinal dorsal horn were studied using 45Ca2+ as a tracer. hCGRP promoted the influx of 45Ca2+ into synaptosomes of the spinal dorsal horn, in a dose dependent manner (at dose ranges from 10(-9) to 10(-6) M). The maximum effect of hCGRP on 45Ca2+ influx was achieved 5 min after addition of the peptide and was significantly inhibited by nifedipine. hCGRP did not alter the influx of 45Ca2+ into synaptosomes of the rat cerebral cortex, a brain area with reportedly few CGRP binding sites. In measurements of the 45Ca2+ efflux from synaptosomes of the spinal dorsal horn, 10(-7) M of hCGRP had no effect on the efflux of 45Ca2+ from the resting synaptosomes, but there was significant inhibitory effect on synaptosomes depolarized by 40 mM K+. The inhibitory effect of hCGRP on the efflux of 45Ca2+ was completely abolished by lowering the incubation temperature of the medium to 0 degrees C. The inhibitory effect of hCGRP on the efflux of 45Ca2+ was not observed in synaptosomes of the cerebral cortex. These findings suggest that hCGRP increases the levels of Ca2+ level in synaptosomes of the spinal dorsal horn, through interactions with its own receptors and the release of neurotransmitters from the nerve terminals is thus enhanced.