Natriuretic peptide receptors on rat thymocytes: inhibition of proliferation by atrial natriuretic peptide

Because the thymus expresses the natriuretic peptides (NP) as well as their respective receptors, an involvement of NP in the physiology of this organ has been suggested. To evaluate functional aspects of NP in the thymus, we looked for thymic cells bearing NP receptors (Npr). Furthermore, the regulation of Npr expression by activation of cells and the influence of NP on the proliferation of thymocytes was studied. Expression of receptor messenger RNAs (mRNAs) was examined by PCR and Northern blot. Existence of functional Npr was confirmed by measurement of cGMP, the second messenger of NP. Proliferation of thymocytes upon concanavalin A (Con A) stimulation was analyzed by incorporation of [3H]thymidine. We report her that thymocytes express mRNAs for the three Npr, namely Npra, Nprb, and Nprc and that activation of Npra and Nprb increases cGMP levels. Stimulation of thymocytes with Con A (1 microgram/ml, 48 h) resulted in an increase of mRNA coding for Npra, the receptor specific for atrial natriuretic peptide (ANP) and brain natriuretic peptide. Nprb and Nprc receptor expression was not altered under these conditions. In agreement with these data only ANP, but not the C-type natriuretic peptide, elicited increased cGMP response in Con A-stimulated cells. ANP inhibited also the proliferation of Con A stimulated thymocytes, whereas C-type natriuretic peptide did not show this effect. These results suggest that ANP affects the complex mechanisms of thymocyte proliferation and differentiation.