Calcitonin gene-related peptide induces the formation of second messengers in primary cultures of neonatal rat spinal cord

This study investigated second messengers formed in response to calcitonin gene-related peptide (CGRP) in primary cultures of neonatal rat spinal cord. CGRP increased the level of cAMP above basal levels (50 pmol/mg protein) over a large range of concentrations. The concentration-response curve had an intermediate plateau at 180 pmol cAMP/mg protein in response to 0.01-0.1 nM CGRP and a maximal plateau of 850 pmol cAMP/mg protein at 300 nM CGRP. The biphasic concentration-response curve (EC₅₀s of 0.7 pM and 22 nM) suggests activation of high- and low-affinity receptors for CGRP. Both neurons and nonneuronal cells contributed to the increase in cAMP formation in response to CGRP. The CGRP receptor blocker, CGRP_8-37, inhibited the response to both 1 and 100 nM CGRP, providing additional support for the hypothesis that both high- and low-affinity receptors mediate the formation of cAMP. Only a high concentration of CGRP (1 μM) increased the formation of cGMP, and CGRP had no effect on the formation of inositol phosphates at any of the concentrations tested (0.1-1 μM). These results suggest that CGRP- induced responses in the spinal cord are mediated predominately via the formation of cAMP. The observation that both neurons and nonneuronal cells responded to CGRP indicate that this peptide may have multiple actions in the spinal cord.