Calcitonin gene-related peptide modulates calcium mobilization in synaptosomes of rat spinal dorsal horn

Effects of synthetic human calcitonin gene-related peptide (hCGRP) on Ca 2+ mobilization in crude synaptosomes prepared from rat spinal dorsal horn were studied using 45Ca 2+ as a tracer. hCGRP promoted the influx of 45Ca 2+ 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 45Ca 2+ influx was achieved 5 min after addition of the peptide and was significantly inhibited by nifedipine. hCGRP did not alter the influx of 45Ca 2+ into synaptosomes of the rat cerebral cortex, a brain area with reportedly few CGRP binding sites. In measurements of the 45Ca 2+ efflux from synaptosomes of the spinal dorsal horn, 10 −7 M of hCGRP had no effect on the efflux of 45Ca 2+ from the resting synaptosomes, but there was significantly inhibitory effect on synaptosomes depolarized by 40 mM K +. The inhibitory effect of hCGRP on the efflux of 45Ca 2+ was completely abolished by lowering the incubation temperature of the medium to 0 °C. The inhibitory effect of hCGRP on the efflux of 45Ca 2+ was not observed in synaptosomes of the cerebral cortex. These findings suggest that hCGRP increases the levels of Ca 2+ 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.