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Institut National de la Santé et de la Recherche Médicale, Unit 482, Signalisation et Fonctions Cellulaires, Applications au Diabète et aux Cancers Digestifs, Hôpital Saint-Antoine, Paris, France; and
Laboratoire d’Immunologie, Centre National de la Recherche Scientifique-Unité Propre de Recherche et de l’Enseignement Supérieur Associée, Hôpital Marie Lannelongue, Le Plessis-Robinson, France
The molecular and functional expression of serpentine membrane
receptors for vasoactive intestinal peptide (VIP), calcitonin
gene-related peptide (CGRP), and calcitonin (CT) were characterized in
human thymus and thymomas from myasthenia gravis (MG) patients and
thymic epithelial cells either in primary culture (PTEC) or transformed
by the siman virus 40 large T (SV40LT) oncogene (LT-TEC). Using
RT-PCR combined with Southern analysis, we identified the PCR products
corresponding to the receptor (-R) transcripts for VIP, CGRP, and CT in
thymus from control subjects and MG patients with either hyperplasia or
thymoma. Similar expressions of the VIP- and CGRP-R transcripts 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
lower intensity than those in control and MG thymus. In agreement with
our molecular analysis, 1) VIP was the most potent peptide among
VIP-related peptides (VIP > PACAP > PHM > PHV) to
stimulate cAMP production through specific type 1 VIP receptors in both
PTEC and LT-TEC; 2) cAMP generation was induced 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 epithelial cells; and 4) in
parallel, the transcription of the acetylcholine receptor 
subunit
(the main autoantigen in MG) was induced by CGRP and CT in PTEC and
LT-TEC, respectively. Our data suggest that the neuroendocrine peptides
VIP, CGRP, and CT may exert functional roles during MG and malignant
transformation of the human thymus.
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