Presence of calcitonin gene-related peptide receptors coupled to adenylate cyclase in human gliomas.

Eleven surgical samples of gliomas (1 of grade II, 3 of grade III and 7 of grade IV) were analyzed. Calcitonin gene-related peptide (CGRP) receptors were identified by 125I-alpha h-CGRP binding in 9 cases and the presence of a CGRP-stimulated adenylate cyclase in all the 11 cases. Tracer binding was inhibited by unlabelled alpha h-CGRP (Kd of 0.3 nM), by (8-37) alpha h-CGRP (Kd of 30 nM), by (12-37) alpha h-CGRP (Kd of 3.000 nM) but not by human calcitonin. The mean density of CGRP receptors (120 fmol/mg membrane protein) was comparable to that of beta-adrenergic receptors. CGRP stimulated 1.4 to 4.7-fold (mean 2.7) the adenylate cyclase activity with a K(act) of 2.0 nM. The CGRP fragments had no intrinsic activity but inhibited the CGRP effect. The (8-37)CGRP fragment had a Ki of 30 nM. Thus, at variance with previous reports on rat and human brain membranes, that showed the presence of CGRP receptors not coupled to adenylate cyclase, we observed in human gliomas the presence of CGRP receptors that, when occupied, stimulated efficiently the adenylate cyclase activity.