Calcitonin gene-related peptide receptors in pig spleen and the involvement of the CGRP(1)receptor in the splenocyte function

Calcitonin gene-related peptide (CGRP)-positive nerve fibers have been found in the trabecula and parenchyme area of pig spleen. Receptor studies have demonstrated that the CGRP binding site in pig spleen membranes has an average K(d)2.24 +/- 0.48 nM and B(max)78 +/- 4.09 fmol/mg of protein. In the K(d)range demonstrated in the binding studies, the dose-dependent suppressive effect of CGRP on spleen T lymphocyte proliferation was found with the maximal effect in 10(-9)M concentration. The same effect, but in a different concentration, was found on peripheral blood T lymphocytes with the maximum in 10(-6)M concentration. Contrary to the results obtained through the simultaneous presence of CGRP and mitogen, preincubation with CGRP led to a stimulation of peripheral blood lymphocytes in response to ConA and had no effect on spleen T lymphocytes. These results illustrate the difference in CGRP effect between lymphocytes of different origins. Using CGRP(1)receptor antagonist CGRP(8-37), we established that the CGRP suppressive effect on spleen T lymphocyte proliferation is CGRP(1)-receptor mediated.