Effects of calcitonin gene-related peptide (CGRP), neurokinin A and neurokinin A (4-10) on the mitogenic response of human peripheral blood mononuclear cells.

(1) We have studied the ability of some regulatory peptides to induce a mitogenic (incorporation of tritiated thymidine) response in human peripheral blood mononuclear cells (PBMC) and to modify the response produced by phytohaemagglutinin (PHA), a well known PBMC mitogen. (2) Human calcitonin gene-related peptide (hCGRP), human or salmon calcitonin (hCT, sCT), neurokinin A (NKA) and neurokinin (4-10) (up to 1 microM for each peptide) did not produce per se any significant PBMC stimulation. (3) hCGRP (0.1 nM-1 microM) produced a concentration dependent enhancement of the response to a submaximal concentration of PHA (1 microgram/ml). On the other hand, hCGRP decreased the mitogenic response to a maximal concentration of PHA (25 micrograms/ml). (4) Neither hCT nor sCT (0.1 nM-1 microM) had a significant influence on the response to PHA (1-25 micrograms/ml). (5) Both NKA and NKA (4-10) produced a concentration-dependent (1 fM-10 pM) enhancement of the response to 1 microgram/ml PHA, while these compounds had no effect on the response to 25 micrograms/ml PHA. (6) These findings suggest a potent modulatory action of CGRP and NKA, two peptides present in sensory and other nerves, on immune function which is possibly mediated via C2 receptors for CGRP and NK-2 tachykinin receptors, respectively.