Functional expression of receptors for calcitonin gene-related peptide, calcitonin, and vasoactive intestinal peptide in the human thymus and thymomas from myasthenia gravis patients

The molecular and functional expression of serpentine membrane receptors fo r vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGR P), and calcitonin (CT) were characterized in human thymus and thymomas fro m myasthenia gravis (MG) patients and thymic epithelial cells either in pri mary culture (PTEC) or transformed by the siman virus 40 large T (SV40LT) o ncogene (LT-TEC), Using RT-PCR combined with Southern analysis, we identifi ed the PCR products corresponding to the receptor (-R) transcripts for VIP, CGRP, aad CT in thymus from control subjects and MG patients with either h yperplasia or thymoma, Similar expressions of the VIP- and CGRP-R transcrip ts were observed in PTEC, whereas the CT-R message was not detected. In LT- TEC, the signals for VIP-R, CGRP-R, and CT-R transcripts were seen with a l ower intensity than those in control and MG thymus, In agreement with our m olecular analysis, 1) VIP was the most potent peptide among VIP-related pep tides (VIP > PACAP > PHM > PBV) to stimulate cAMP production through specif ic type 1 VIP receptors in both PTEC and LT-TEC; 2) cAMP generation was ind uced by CGRP in PTEC and by CT in LT-TEC; 3) in frozen thymic sections and by flow cytometry, type 1 VIP-R, CGRP-R, and CT-R were localized in epithel ial cells; and 4) in parallel, the transcription of the acetylcholine recep tor cr subunit (the main autoantigen in MG) was induced by CGRP and CT in P TEC and LT-TEC, respectively. Our data suggest that the neuroendocrine pept ides VIP, CGRP, and CT may exert functional roles during MG and malignant t ransformation of the human thymus.