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) r eceptors were identified by I-125-alpha h-CGRP binding in 9 cases and the presence of a CGRP-stimulated adenylate cyclase in all the 11 case s. Tracer binding was inhibited by unlabelled ah-CGRP (K-d of 0.3 nM), by (8-37)alpha h-CGRP (K-d of 30 nM), by (12-37)alpha h-CGRP (K-d of 3.000 nM) but not by human calcitonin. The mean density of CGRP recept ors (120 fmol/mg membrane protein) was comparable to that of P-adrener gic receptors. CGRP stimulated 1.4 to 4.7-fold (mean 2.7) the adenylat e cyclase activity with a K-act of 2.0 nM. The CGRP fragments had no i ntrinsic activity but inhibited the CGRP effect. The (8-37)CGRP fragme nt had a Ki of 30 nM. Thus, at variance with previous reports on rat a nd human brain membranes, that showed the presence of CGRP receptors n ot coupled to adenylate cyclase, we observed in human gliomas the pres ence of CGRP receptors that, when occupied, stimulated efficiently the adenylate cyclase activity.